Cells that migrate as collectives help establish and organize many tissues and organs in the embryo, yet also promote tumor invasion, dissemination and metastasis (Friedl et al., 2012; Friedl and Gilmour, 2009; Wang et al., 2016; Cheung and Ewald, 2016; Scarpa and Mayor, 2016). A wide variety of cells undergo collective cell migration during development, ranging from neural crest cells in Xenopus, the zebrafish lateral line primordium, and branching mammary glands (Friedl and Gilmour, 2009; Scarpa and Mayor, 2016; Huebner et al., 2016; Shellard and Mayor, 2019), among many other examples. Despite the apparent diversity in collectively migrating cell types, there is remarkable conservation of the cellular and molecular mechanisms that underlie group cell movements. In particular, migrating collectives require fine-tuned organization and cell coordination to move effectively as a unified group. Similar to individually migrating cells, collectively migrating cells display a front-rear polarity, but this polarity is often organized at the group level (Mayor and Etienne-Manneville, 2016). Leader cells at the front extend characteristic protrusions that help collectives navigate tissues. Mechanical cell coupling and biochemical signals then reinforce collective polarity by actively repressing protrusions from follower cells and by maintaining lead cell protrusions that pull the group forward (Mayor and Etienne-Manneville, 2016; Friedl and Mayor, 2017). Importantly, cell-cell adhesions keep collectives together by maintaining strong but flexible connections between cells. Moreover, many cell collectives exhibit a ‘supracellular’ organization of the cytoskeleton at the outer perimeter of the entire cell group that serves to further coordinate multicellular movement (Shellard and Mayor, 2019; Shellard et al., 2018; Hidalgo-Carcedo et al., 2011; Reffay et al., 2014). Despite progress in understanding how single cells become polarized and motile, less is known about the mechanisms that control the global organization, cohesion, and coordination of cells in migrating collectives.

Drosophila border cells are a genetically tractable and relatively simple model well-suited to investigate how cell collectives undergo polarized and cooperative migration within a developing tissue (Montell et al., 2012; Saadin and Starz-Gaiano, 2016). The Drosophila ovary is composed of strings of ovarioles made up of developing egg chambers, the functional unit of the Drosophila ovary. During late oogenesis, four to eight follicle cells are specified at the anterior end of the egg chamber to become migratory border cells. The border cells then surround a specialized pair of follicle cells, the polar cells, and delaminate as a multicellular cluster from the follicular epithelium. Subsequently, the border cell cluster undergoes a stereotyped collective migration, moving between 15 large germline-derived nurse cells to eventually reach the oocyte at the posterior end of the egg chamber (Figure 1A–F). Throughout migration, individual border cells maintain contacts with each other and with the central polar cells so that all cells move as a single cohesive unit (Llense and Martín-Blanco, 2008; Cai et al., 2014). A leader cell at the front extends a migratory protrusion whereas protrusions are suppressed in trailing follower cells (Prasad and Montell, 2007; Bianco et al., 2007; Poukkula et al., 2011). As with other collectives, polarization of the border cell cluster is critical for the ability to move together and in the correct direction, in this case towards the oocyte (Figure 1A–F; Prasad and Montell, 2007; Bianco et al., 2007).

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Polarization of the border cell cluster begins when two receptor tyrosine kinases (RTKs) expressed by border cells, PDGF- and VEGF-receptor related (PVR) and Epidermal Growth Factor Receptor (EGFR), respond to multiple growth factors secreted from the oocyte (Duchek et al., 2001; McDonald et al., 2006). Signaling through PVR/EGFR increases activation of the small GTPase Rac, triggering F-actin polymerization and formation of a major protrusion in the lead border cell (Prasad and Montell, 2007; Poukkula et al., 2011; Duchek et al., 2001; Wang et al., 2010). E-Cadherin-based adhesion to the nurse cell substrate stabilizes this lead cell protrusion via a feedback loop with Rac (Cai et al., 2014). Furthermore, the endocytic protein Rab11 and the actin-binding protein Moesin mediate communication between border cells to restrict Rac activation to the lead cell (Ramel et al., 2013). Mechanical coupling of border cells through E-Cadherin suppresses protrusions in follower cells, both at cluster exterior surfaces but also between border cells and at contacts with polar cells (Montell et al., 2012; Cai et al., 2014). E-Cadherin also maintains border cell attachment to the central polar cells. F-actin and non-muscle myosin II (Myo-II) are enriched at the outer edges of the border cell cluster (Aranjuez et al., 2016; Lucas et al., 2013; Combedazou et al., 2017). Such ‘inside-outside’ polarity contributes to the overall cluster shape, cell-cell organization, and coordinated motility of all border cells (Montell et al., 2012). While progress has been made in understanding the establishment of front-rear polarity, much less is known about how individual border cell behaviors are fine-tuned and adjusted to produce coordinated and cooperative movement of the cluster as an entire unit.

In the current study we made the unexpected discovery that Protein phosphatase 1 (Pp1) activity coordinates the collective behavior of individual border cells. Dynamic cycles of protein phosphorylation and dephosphorylation precisely control many signaling, adhesion and cytoskeletal pathways required for cell migration (Larsen et al., 2003). Serine-threonine kinases, such as Par-1, Jun kinase (JNK), and the p21-activated kinase Pak3, as well as phosphorylated substrate proteins such as the Myo-II regulatory light chain (MRLC; Drosophila Spaghetti squash, Sqh) and Moesin regulate different aspects of border cell migration (Llense and Martín-Blanco, 2008; Ramel et al., 2013; Majumder et al., 2012; Felix et al., 2015). In contrast, the serine-threonine phosphatases that counteract these and other kinases and phosphorylation events have not been extensively studied, either in border cells or in other cell collectives. Pp1 is a highly conserved and ubiquitous serine-threonine phosphatase found in all eukaryotic cells (Lin et al., 1999; Verbinnen et al., 2017). Pp1 can directly dephosphorylate substrates in vitro, but specificity for phosphorylated substrates in vivo is generally conferred by a large number of regulatory subunits (also called Pp1-interacting proteins [PIPs]). These regulatory subunits form functional Pp1 complexes through binding to the Pp1 catalytic (Pp1c) subunits and mediate the recruitment of, or increase the affinity for, particular substrates (Verbinnen et al., 2017; Heroes et al., 2013). Thus, despite the potential for pleiotropy, Pp1 complexes have specific and precise cellular functions in vivo, that range from regulation of protein synthesis, cell division and apoptosis to individual cell migration (Ceulemans and Bollen, 2004; Ferreira et al., 2019).

We now show that Pp1 activity controls multiple collective behaviors of border cells, including timely delamination from the epithelium, collective polarization, cohesion, cell-cell coordination, and migration. Remarkably, Pp1-inhibited border cells round up, break off from the main group, and move as single cells or small groups but are generally unable to complete their migration. We determine that Pp1 controls the levels of E-Cadherin and β-Catenin, which are needed to retain border cells within a cohesive cluster. Additionally, Pp1 activity restricts F-actin and Myo-II enrichment to the outer edges of the cluster, maintaining a supracellular cytoskeletal ultrastructure and supporting polarized collective movement. Furthermore, a major Pp1 specific complex for Myo-II activity, myosin phosphatase, coordinates border cell shape and adherence of cells to the cluster. Our work thus identifies Pp1 activity, mediated through distinctive phosphatase complexes such as myosin phosphatase, as a critical molecular regulator of collective cell versus single cell behaviors in a developmentally migrating collective.

To migrate collectively, cells need to coordinate and cooperate at the multicellular level. Individual cells within a group must remain together, maintain optimal cell shapes, organize motility of neighboring cells, and polarize. The mechanisms that globally orchestrate single cell behaviors within migrating cell collectives are still unclear. Here we report that Pp1 activity is a critical regulator of key intra- and intercellular mechanisms that together produce collective border cell migration. Loss of Pp1 activity, through overexpression of NiPp1 or Pp1c RNAi, switches border cells from migrating as a cohesive cluster to moving as single cells or in small groups (Figure 8A). A critical aspect of this switch is the redistribution of enriched F-actin and Myo-II to cell contacts between individual border cells, rather than at the cluster periphery, and a concomitant loss of adhesion between cells. We identified one key Pp1 phosphatase complex, myosin phosphatase, that controls collective-level myosin contraction (Figure 8B). Additional phosphatase complexes, through as-yet-unknown regulatory subunits, likely function in border cells to generate collective F-actin organization, maintain cell-cell adhesions, and potentially to restrain overall RhoA activity levels. Our results support a model in which balanced Pp1 activity promotes collective border cell cluster migration, and timely delamination from the epithelium, by coordinating single border cell motility and keeping the cells together (Figure 8A).

Figure 8

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Many collectively migrating cells require a supracellular enrichment of actomyosin at the group perimeter to help organize their movement (Shellard and Mayor, 2019; Shellard et al., 2018; Hidalgo-Carcedo et al., 2011; Reffay et al., 2014). Active Myo-II is required for border cell collective detachment from the epithelium, cluster shape, rotational movement of the cluster, and normal protrusion dynamics (Aranjuez et al., 2016; Combedazou et al., 2017; Majumder et al., 2012; Mishra et al., 2019; Fulga and Rørth, 2002). We show here that Pp1 organizes collective-level Myo-II-contractility during border cell migration. Inhibition of Pp1 shifts the balance of dynamic activated Myo-II from the cluster-level to individual border cells, resulting in rounded, hyper-contractile border cells that dissociate from the cluster. The myosin-specific Pp1 complex, myosin phosphatase, directly dephosphorylates Sqh and inhibits Myo-II activation (Grassie et al., 2011). Depletion of Mbs, the myosin-binding regulatory subunit of myosin phosphatase, causes rounder border cells and fragmentation of the cluster. We previously found that Mbs-deficient border cells have significantly higher levels of phosphorylated Sqh (p-Myo-II) (Majumder et al., 2012). Thus, myosin phosphatase inhibits Myo-II activation to promote coordinated collective contractility of border cells. Myosin phosphatase is a downstream target of Rok, which phosphorylates and inhibits the Mbs subunit (Kimura et al., 1996). Consistent with loss of myosin phosphatase activity, Pp1-inhibition increases phosphorylated active Sqh in individual border cells within the cluster. Thus, myosin phosphatase, downstream of Rok, promotes elevated active Myo-II (p-Sqh/p-Myo-II) and cortical contraction of the entire collective (Figure 8B). Interestingly, expression of constitutively activated RhoA also induces cellular hypercontractility, resulting in amoeboid-like round border cells (Aranjuez et al., 2016; Combedazou et al., 2017; Mishra et al., 2019). RhoA activates Rok, which directly phosphorylates and activates the Myo-II regulatory subunit Sqh (Amano et al., 1996; Matsui et al., 1996). We observe somewhat elevated RhoA activity in the absence of Pp1 activity. Thus, Pp1 may also restrain the overall levels of RhoA activity in border cells through an unknown Pp1 complex, which would further promote the collective actomyosin contraction of border cells (Figure 8B).

Myo-II is activated preferentially at the cluster periphery and not between internal border cell contacts. Mbs and at least one catalytic subunit, Flw, localize uniformly in border cells, both on the cluster perimeter and between cells. Such uniform phosphatase distribution would be expected to dephosphorylate and inactivate Myo-II everywhere, yet phosphorylated Sqh is only absent from internal cluster border cell contacts. Rok phosphorylates and inactivates Mbs in addition to directly activating Myo-II (Kimura et al., 1996). Our previous results indicate that Rok localizes to the cluster perimeter similar to p-Sqh, but there appeared to be overall less Rok between border cells (Aranjuez et al., 2016). Thus, spatially localized Rok could inhibit myosin phosphatase and activate Myo-II preferentially at the outer edges of the cluster (Figure 8A). Other mechanisms likely contribute to collective polarization of Myo-II. For example, during border cell detachment from the epithelium the polarity kinase Par-1 phosphorylates and inactivates Mbs at the cluster rear resulting in increased active Myo-II, whereas the Hippo pathway prevents accumulation of phosphorylated Myo-II between border cells (Lucas et al., 2013; Majumder et al., 2012).

Our data also support a role for Pp1 in controlling F-actin stability, dynamics, and spatial organization. Similar to the pattern of activated Myo-II, cortical F-actin is normally high at the cluster periphery, although low levels are found between border cells (Ramel et al., 2013; Lucas et al., 2013; Wang et al., 2018). Reduced Pp1 activity causes high levels of F-actin to redistribute from the cluster perimeter to surround entire cell cortices of individual border cells. In migrating cells, networks of F-actin produce forces essential for protrusion extension and retraction dynamics that generate forward movement (Ridley, 2011; Caswell and Zech, 2018). Further supporting a role for Pp1 in regulating F-actin, Pp1-inhibited border cells extend fewer protrusions with shorter lifetimes, resulting in altered motility patterns. How Pp1 promotes F-actin organization and dynamics is unknown. One possibility comes from the known function for Rok in regulating F-actin through the downstream effector LIM Kinase (LIMK) (Julian and Olson, 2014). LIMK phosphorylates and inhibits cofilin, an actin severing and depolymerizing factor (Bravo-Cordero et al., 2013). In border cells, cofilin restrains F-actin levels throughout the cluster and increases actin dynamics, resulting in normal cluster morphology and major protrusion formation (Zhang et al., 2011). Although cofilin dephosphorylation, and thus activation, is typically mediated by the dual-specificity phosphatase Slingshot (Bravo-Cordero et al., 2013), Pp1-containing complexes have been shown to dephosphorylate cofilin in a variety of cell types (Huet et al., 2013; Ambach et al., 2000; Zhang et al., 2012; Oleinik et al., 2010). Additionally, RhoA activates formin proteins such as Diaphanous, which nucleate actin to form long filaments (Kühn and Geyer, 2014). There are at least seven formin-related proteins in Drosophila, several of which have domains associated with activation by Rho GTPases. However, which formin, if any, promotes border cell migration and F-actin distribution is unknown. Further work will be needed to determine whether any of these potential targets, or other actin regulatory proteins, control collective level F-actin enrichment via Pp1.

A major consequence of decreased Pp1 activity is fragmentation of the border cell cluster into single border cells and small groups. This raises the question of how Pp1 activity maintains cluster cohesion, which is critical for collective cell movement in vivo. Like many cell collectives, high levels of cadherin-catenin complex proteins are detected between all border cells (Niewiadomska et al., 1999). The cadherin-catenin complex is required for border cells to adhere to the central polar cells as well as to provide migratory traction of the entire cluster upon the nurse cells (Cai et al., 2014; Niewiadomska et al., 1999). We found that Pp1 maintains E-Cadherin and β-Catenin levels between border cells. Indeed, other mutants that disrupt the levels and localization of adhesion proteins in border cells often also disrupt cluster shape and cohesion. For example, loss of JNK signaling causes border cell clusters to dramatically elongate, with downregulation of adhesion resulting in incomplete separation of border cells (Llense and Martín-Blanco, 2008; Melani et al., 2008). Raskol, a putative Ras guanine nucleotide activating protein (GAP), maintains E-cadherin at BC-BC contacts and cohesion of the cluster (Raza et al., 2019). However, while loss of Raskol causes a significant number of border cells to fully dissociate from the cluster (~35%) (Raza et al., 2019), similar to what we observe with knockdown of the cadherin-catenin complex, this is less than what we observe upon inhibition of Pp1 activity (~90%). Thus, while cluster fragmentation caused by Pp1 inhibition is at least partly due to deficient cadherin-catenin adhesion, other targets likely contribute.

Our results indicate that E-Cadherin, β-Catenin, and α-Catenin maintain adhesion of border cells to each other in addition to known roles in keeping border cells attached to the polar cells (Cai et al., 2014). Knockdown of the cadherin-catenin complex members in both border cells and polar cells causes border cells to significantly dissociate from the cluster. The requirement in border cells for cadherin-catenin in cluster cohesion may have been masked in prior studies due to the inability of strong loss-of-function cadherin-catenin mutant border cells to move at all (Cai et al., 2014; Niewiadomska et al., 1999; Sarpal et al., 2012; Desai et al., 2013). While RNAi for E-Cadherin, β-Catenin, and α-Catenin each strongly knock down the respective protein levels, it may be that a small amount of each protein is still present. Such remaining cadherin-catenin proteins may provide just enough traction for border cells to partially migrate upon the nurse cells. We speculate that movement of cadherin-catenin-deficient border cells within the confining tissue would provide mechanical stresses that break the cluster apart at weakened border cell-border cell contacts. Indeed, a mutant α-Catenin protein that lacks part of the C-terminal F-actin-binding domain was shown to partially rescue the migration defects caused by loss of α-Catenin; however, these rescued border cell clusters split into several parts along the migration path (Desai et al., 2013). Further supporting this idea, Pp1-inhibited border cells fall apart during their effort to migrate between the nurse cells.

How do Pp1 phosphatase complexes molecularly promote cluster cohesion? Given the effects of Pp1 on E-Cadherin and β-Catenin at internal border cell contacts, and the requirement for cadherin-catenin complex proteins in maintaining cluster integrity, Pp1 could directly regulate cadherin-catenin protein stability and/or adhesive strength. In mammalian and Drosophila cells, phosphorylation of a conserved stretch of serine residues in the E-Cadherin C-terminal tail region regulates E-Cadherin protein stability, binding of E-Cadherin to β-Catenin, and cell-cell junction formation and turnover (Stappert and Kemler, 1994; McEwen et al., 2014; Chen et al., 2017). Serine-phosphorylation of α-Catenin is also required for adhesion between epithelial cells and possibly for efficient border cell migration (Escobar et al., 2015). More work will be needed to determine whether a to-be-identified Pp1-containing phosphatase complex directly dephosphorylates E-Cadherin and/or α-Catenin, as the roles for phosphatases in cadherin-catenin junctional stability are still poorly understood.

Alternatively, or in addition, Pp1-dependent restriction of collective actomyosin contraction to the cluster periphery could allow internal cluster cell-cell junctions to be maintained. Pp1-inhibition greatly alters actomyosin distribution, causing individual border cells to contract and round up. The forces transmitted by high cell contractility alone could weaken adherens junctions, causing the border cells to break apart during migration (Figure 8A). Myosin phosphatase-depleted border cells, which have elevated phosphorylated Sqh (Majumder et al., 2012), and thus active Myo-II, are round, highly contractile, and fall off the cluster. In support of this idea, overexpression of a phosphorylation mutant form of Sqh (Sqh^E20E21), which mimics activated Myo-II, causes border cells to have a similar round shape and separate from the cluster (Mishra et al., 2019). Thus, collective-level active actomyosin contraction contributes to keeping border cells adhered to the cluster. Myo-II and cadherin-catenin complexes have dynamic and quite complex interactions that influence stability of cell-cell junctions, and which may depend on cellular context (Mège and Ishiyama, 2017; Yap et al., 2018). In border cells, the cadherin-catenin complex promotes enrichment of actomyosin to the cluster periphery, whereas Myo-II does not greatly influence cadherin-catenin levels within the cluster (this study) (Mishra et al., 2019). However, Pp1 is required for the proper distribution (or stability) of cadherin-catenin at cell contacts between border cells and prevents the enrichment of actomyosin in individual border cells. Moreover, NiPp1 expression disrupts cluster cohesion to a greater extent than knockdown of either myosin phosphatase or cadherin-catenin complex members alone. This suggests that cadherin-catenin stability and optimal collective-wide actomyosin activity both contribute to cluster cohesion through distinct Pp1 phosphatase complexes, although this possibility remains to be formally tested (Figure 8B).

Our study implicates Pp1 as a major regulator of collective cohesion and migration in border cells. Pp1 catalytic subunits and their regulatory subunits are conserved across eukaryotes (Lin et al., 1999; Verbinnen et al., 2017; Heroes et al., 2013; Ferreira et al., 2019). The roles of specific Pp1 complexes in collective cell migration during development and in cancer have not been well studied. Intriguingly, Mypt1 (Mbs homolog) promotes polarized mesodermal migration during zebrafish gastrulation (Weiser et al., 2009). Similar to what we observe in Mbs-depleted border cells, inhibition of zebrafish Mypt1 switched cells from an elongated mesenchymal mode of migration to a hyper-contractile amoeboid mode of migration. Another Pp1 phosphatase complex containing the Phactr4 (phosphatase and actin regulator 4) regulatory subunit promotes the chain-like collective migration of enteric neural crest cells, which colonize the gut and form the enteric nervous system during development (Zhang et al., 2012). Phactr4, through Pp1, specifically controls the directed migration and shape of enteric neural crest cells through integrin, Rok, and cofilin. Given the conservation of these and other phosphatase complexes, our study highlights the importance of balanced Pp1 phosphatase activity in the organization and coordination of migrating cell collectives.

All data generated or analysed during this study are included in the manuscript and supporting files.

1. 1. Amano M
   2. Ito M
   3. Kimura K
   4. Fukata Y
   5. Chihara K
   6. Nakano T
   7. Matsuura Y
   8. Kaibuchi K

   (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase)

   Journal of Biological Chemistry 271:20246–20249.

   https://doi.org/10.1074/jbc.271.34.20246

   • PubMed
   • Google Scholar
2. 1. Ambach A
   2. Saunus J
   3. Konstandin M
   4. Wesselborg S
   5. Meuer SC
   6. Samstag Y

   (2000) The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes

   European Journal of Immunology 30:3422–3431.

   https://doi.org/10.1002/1521-4141(2000012)30:12<3422::AID-IMMU3422>3.0.CO;2-J

   • PubMed
   • Google Scholar
3. 1. Aranjuez G
   2. Burtscher A
   3. Sawant K
   4. Majumder P
   5. McDonald JA

   (2016) Dynamic myosin activation promotes collective morphology and migration by locally balancing oppositional forces from surrounding tissue

   Molecular Biology of the Cell 27:1898–1910.

   https://doi.org/10.1091/mbc.e15-10-0744

   • PubMed
   • Google Scholar
4. 1. Bennett D
   2. Szöor B
   3. Gross S
   4. Vereshchagina N
   5. Alphey L

   (2003)

   Ectopic expression of inhibitors of protein phosphatase type 1 (PP1) can be used to analyze roles of PP1 in Drosophila development

   Genetics 164:235–245.

   • PubMed
   • Google Scholar
5. 1. Bianco A
   2. Poukkula M
   3. Cliffe A
   4. Mathieu J
   5. Luque CM
   6. Fulga TA
   7. Rørth P

   (2007) Two distinct modes of guidance signalling during collective migration of border cells

   Nature 448:362–365.

   https://doi.org/10.1038/nature05965

   • PubMed
   • Google Scholar
6. 1. Bischof J
   2. Björklund M
   3. Furger E
   4. Schertel C
   5. Taipale J
   6. Basler K

   (2013) A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila

   Development 140:2434–2442.

   https://doi.org/10.1242/dev.088757

   • PubMed
   • Google Scholar
7. 1. Bravo-Cordero JJ
   2. Magalhaes MA
   3. Eddy RJ
   4. Hodgson L
   5. Condeelis J

   (2013) Functions of cofilin in cell locomotion and invasion

   Nature Reviews Molecular Cell Biology 14:405–415.

   https://doi.org/10.1038/nrm3609

   • PubMed
   • Google Scholar
8. 1. Cai D
   2. Chen SC
   3. Prasad M
   4. He L
   5. Wang X
   6. Choesmel-Cadamuro V
   7. Sawyer JK
   8. Danuser G
   9. Montell DJ

   (2014) Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration

   Cell 157:1146–1159.

   https://doi.org/10.1016/j.cell.2014.03.045

   • PubMed
   • Google Scholar
9. 1. Caswell PT
   2. Zech T

   (2018) Actin-Based cell protrusion in a 3D matrix

   Trends in Cell Biology 28:823–834.

   https://doi.org/10.1016/j.tcb.2018.06.003

   • PubMed
   • Google Scholar
10. 1. Ceulemans H
    2. Bollen M

    (2004) Functional diversity of protein phosphatase-1, a cellular economizer and reset button

    Physiological Reviews 84:1–39.

    https://doi.org/10.1152/physrev.00013.2003

    • PubMed
    • Google Scholar
11. 1. Chen YJ
    2. Huang J
    3. Huang L
    4. Austin E
    5. Hong Y

    (2017) Phosphorylation potential of Drosophila E-Cadherin intracellular domain is essential for development and adherens junction biosynthetic dynamics regulation

    Development 144:1242–1248.

    https://doi.org/10.1242/dev.141598

    • PubMed
    • Google Scholar
12. 1. Cheung KJ
    2. Ewald AJ

    (2016) A collective route to metastasis: seeding by tumor cell clusters

    Science 352:167–169.

    https://doi.org/10.1126/science.aaf6546

    • PubMed
    • Google Scholar
13. 1. Collins C
    2. Nelson WJ

    (2015) Running with neighbors: coordinating cell migration and cell-cell adhesion

    Current Opinion in Cell Biology 36:62–70.

    https://doi.org/10.1016/j.ceb.2015.07.004

    • PubMed
    • Google Scholar
14. 1. Combedazou A
    2. Choesmel-Cadamuro V
    3. Gay G
    4. Liu J
    5. Dupré L
    6. Ramel D
    7. Wang X

    (2017) Myosin II governs collective cell migration behaviour downstream of guidance receptor signalling

    Journal of Cell Science 130:97–103.

    https://doi.org/10.1242/jcs.179952

    • PubMed
    • Google Scholar
15. 1. Dai W
    2. Montell DJ

    (2016) Live imaging of border cell migration in Drosophila

    Methods Mol Biol 1407:153–168.

    https://doi.org/10.1007/978-1-4939-3480-5_12

    • Google Scholar
16. 1. Desai R
    2. Sarpal R
    3. Ishiyama N
    4. Pellikka M
    5. Ikura M
    6. Tepass U

    (2013) Monomeric α-catenin links cadherin to the actin cytoskeleton

    Nature Cell Biology 15:261–273.

    https://doi.org/10.1038/ncb2685

    • PubMed
    • Google Scholar
17. 1. Dombrádi V
    2. Axton JM
    3. Brewis ND
    4. da Cruz e Silva EF
    5. Alphey L
    6. Cohen PT

    (1990) Drosophila contains three genes that encode distinct isoforms of protein phosphatase 1

    European Journal of Biochemistry 194:739–745.

    https://doi.org/10.1111/j.1432-1033.1990.tb19464.x

    • PubMed
    • Google Scholar
18. 1. Dombrádi V
    2. Mann DJ
    3. Saunders RD
    4. Cohen PT

    (1993) Cloning of the fourth functional gene for protein phosphatase 1 in Drosophila melanogaster from its chromosomal location

    European Journal of Biochemistry 212:177–183.

    https://doi.org/10.1111/j.1432-1033.1993.tb17648.x

    • PubMed
    • Google Scholar
19. 1. Duchek P
    2. Somogyi K
    3. Jékely G
    4. Beccari S
    5. Rørth P

    (2001) Guidance of cell migration by the Drosophila PDGF/VEGF receptor

    Cell 107:17–26.

    https://doi.org/10.1016/S0092-8674(01)00502-5

    • PubMed
    • Google Scholar
20. 1. Escobar DJ
    2. Desai R
    3. Ishiyama N
    4. Folmsbee SS
    5. Novak MN
    6. Flozak AS
    7. Daugherty RL
    8. Mo R
    9. Nanavati D
    10. Sarpal R
    11. Leckband D
    12. Ikura M
    13. Tepass U
    14. Gottardi CJ

    (2015) α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism

    Journal of Cell Science 128:1150–1165.

    https://doi.org/10.1242/jcs.163824

    • PubMed
    • Google Scholar
21. 1. Felix M
    2. Chayengia M
    3. Ghosh R
    4. Sharma A
    5. Prasad M

    (2015) Pak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis

    Development 142:3692–3703.

    https://doi.org/10.1242/dev.125682

    • PubMed
    • Google Scholar
22. 1. Ferreira M
    2. Beullens M
    3. Bollen M
    4. Van Eynde A

    (2019) Functions and therapeutic potential of protein phosphatase 1: insights from mouse genetics

    Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research 1866:16–30.

    https://doi.org/10.1016/j.bbamcr.2018.07.019

    • Google Scholar
23. 1. Friedl P
    2. Locker J
    3. Sahai E
    4. Segall JE

    (2012) Classifying collective Cancer cell invasion

    Nature Cell Biology 14:777–783.

    https://doi.org/10.1038/ncb2548

    • PubMed
    • Google Scholar
24. 1. Friedl P
    2. Gilmour D

    (2009) Collective cell migration in Morphogenesis, regeneration and Cancer

    Nature Reviews Molecular Cell Biology 10:445–457.

    https://doi.org/10.1038/nrm2720

    • PubMed
    • Google Scholar
25. 1. Friedl P
    2. Mayor R

    (2017) Tuning collective cell migration by Cell-Cell junction regulation

    Cold Spring Harbor Perspectives in Biology 9:a029199.

    https://doi.org/10.1101/cshperspect.a029199

    • PubMed
    • Google Scholar
26. 1. Fulga TA
    2. Rørth P

    (2002) Invasive cell migration is initiated by guided growth of long cellular extensions

    Nature Cell Biology 4:715–719.

    https://doi.org/10.1038/ncb848

    • PubMed
    • Google Scholar
27. 1. Ghiglione C
    2. Devergne O
    3. Georgenthum E
    4. Carballès F
    5. Médioni C
    6. Cerezo D
    7. Noselli S

    (2002) The Drosophila cytokine receptor domeless controls border cell migration and epithelial polarization during oogenesis

    Development 129:5437–5447.

    https://doi.org/10.1242/dev.00116

    • PubMed
    • Google Scholar
28. 1. Grassie ME
    2. Moffat LD
    3. Walsh MP
    4. MacDonald JA

    (2011) The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1δ

    Archives of Biochemistry and Biophysics 510:147–159.

    https://doi.org/10.1016/j.abb.2011.01.018

    • PubMed
    • Google Scholar
29. 1. Graveley BR
    2. Brooks AN
    3. Carlson JW
    4. Duff MO
    5. Landolin JM
    6. Yang L
    7. Artieri CG
    8. van Baren MJ
    9. Boley N
    10. Booth BW
    11. Brown JB
    12. Cherbas L
    13. Davis CA
    14. Dobin A
    15. Li R
    16. Lin W
    17. Malone JH
    18. Mattiuzzo NR
    19. Miller D
    20. Sturgill D
    21. Tuch BB
    22. Zaleski C
    23. Zhang D
    24. Blanchette M
    25. Dudoit S
    26. Eads B
    27. Green RE
    28. Hammonds A
    29. Jiang L
    30. Kapranov P
    31. Langton L
    32. Perrimon N
    33. Sandler JE
    34. Wan KH
    35. Willingham A
    36. Zhang Y
    37. Zou Y
    38. Andrews J
    39. Bickel PJ
    40. Brenner SE
    41. Brent MR
    42. Cherbas P
    43. Gingeras TR
    44. Hoskins RA
    45. Kaufman TC
    46. Oliver B
    47. Celniker SE

    (2011) The developmental transcriptome of Drosophila melanogaster

    Nature 471:473–479.

    https://doi.org/10.1038/nature09715

    • PubMed
    • Google Scholar
30. 1. Heroes E
    2. Lesage B
    3. Görnemann J
    4. Beullens M
    5. Van Meervelt L
    6. Bollen M

    (2013) The PP1 binding code: a molecular-lego strategy that governs specificity

    FEBS Journal 280:584–595.

    https://doi.org/10.1111/j.1742-4658.2012.08547.x

    • PubMed
    • Google Scholar
31. 1. Hidalgo-Carcedo C
    2. Hooper S
    3. Chaudhry SI
    4. Williamson P
    5. Harrington K
    6. Leitinger B
    7. Sahai E

    (2011) Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6

    Nature Cell Biology 13:49–59.

    https://doi.org/10.1038/ncb2133

    • PubMed
    • Google Scholar
32. 1. Hu Y
    2. Flockhart I
    3. Vinayagam A
    4. Bergwitz C
    5. Berger B
    6. Perrimon N
    7. Mohr SE

    (2011) An integrative approach to ortholog prediction for disease-focused and other functional studies

    BMC Bioinformatics 12:357–1100.

    https://doi.org/10.1186/1471-2105-12-357

    • PubMed
    • Google Scholar
33. 1. Huebner RJ
    2. Neumann NM
    3. Ewald AJ

    (2016) Mammary epithelial tubes elongate through MAPK-dependent coordination of cell migration

    Development 143:983–993.

    https://doi.org/10.1242/dev.127944

    • PubMed
    • Google Scholar
34. 1. Huet G
    2. Rajakylä EK
    3. Viita T
    4. Skarp KP
    5. Crivaro M
    6. Dopie J
    7. Vartiainen MK

    (2013) Actin-regulated feedback loop based on Phactr4, PP1 and Cofilin maintains the actin monomer pool

    Journal of Cell Science 126:497–507.

    https://doi.org/10.1242/jcs.113241

    • PubMed
    • Google Scholar
35. 1. Jambor H
    2. Surendranath V
    3. Kalinka AT
    4. Mejstrik P
    5. Saalfeld S
    6. Tomancak P

    (2015) Systematic imaging reveals features and changing localization of mRNAs in Drosophila development

    eLife 4:e05003.

    https://doi.org/10.7554/eLife.05003

    • Google Scholar
36. 1. Julian L
    2. Olson MF

    (2014) Rho-associated coiled-coil containing kinases (ROCK)

    Small GTPases 5:e29846.

    https://doi.org/10.4161/sgtp.29846

    • Google Scholar
37. 1. Kimura K
    2. Ito M
    3. Amano M
    4. Chihara K
    5. Fukata Y
    6. Nakafuku M
    7. Yamamori B
    8. Feng J
    9. Nakano T
    10. Okawa K
    11. Iwamatsu A
    12. Kaibuchi K

    (1996) Regulation of myosin phosphatase by rho and Rho-associated kinase (Rho-kinase)

    Science 273:245–248.

    https://doi.org/10.1126/science.273.5272.245

    • PubMed
    • Google Scholar
38. 1. Kühn S
    2. Geyer M

    (2014) Formins as effector proteins of rho GTPases

    Small GTPases 5:e983876.

    https://doi.org/10.4161/sgtp.29513

    • Google Scholar
39. 1. Larsen M
    2. Tremblay ML
    3. Yamada KM

    (2003) Phosphatases in cell-matrix adhesion and migration

    Nature Reviews Molecular Cell Biology 4:700–711.

    https://doi.org/10.1038/nrm1199

    • PubMed
    • Google Scholar
40. 1. le Duc Q
    2. Shi Q
    3. Blonk I
    4. Sonnenberg A
    5. Wang N
    6. Leckband D
    7. de Rooij J

    (2010) Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner

    The Journal of Cell Biology 189:1107–1115.

    https://doi.org/10.1083/jcb.201001149

    • PubMed
    • Google Scholar
41. 1. Lin Q
    2. Buckler ES
    3. Muse SV
    4. Walker JC

    (1999) Molecular evolution of type 1 serine/threonine protein phosphatases

    Molecular Phylogenetics and Evolution 12:57–66.

    https://doi.org/10.1006/mpev.1998.0560

    • PubMed
    • Google Scholar
42. 1. Llense F
    2. Martín-Blanco E

    (2008) JNK signaling controls border cell cluster integrity and collective cell migration

    Current Biology 18:538–544.

    https://doi.org/10.1016/j.cub.2008.03.029

    • PubMed
    • Google Scholar
43. 1. Lucas EP
    2. Khanal I
    3. Gaspar P
    4. Fletcher GC
    5. Polesello C
    6. Tapon N
    7. Thompson BJ

    (2013) The hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells

    The Journal of Cell Biology 201:875–885.

    https://doi.org/10.1083/jcb.201210073

    • PubMed
    • Google Scholar
44. 1. Majumder P
    2. Aranjuez G
    3. Amick J
    4. McDonald JA

    (2012) Par-1 controls myosin-II activity through myosin phosphatase to regulate border cell migration

    Current Biology 22:363–372.

    https://doi.org/10.1016/j.cub.2012.01.037

    • PubMed
    • Google Scholar
45. 1. Matsui T
    2. Amano M
    3. Yamamoto T
    4. Chihara K
    5. Nakafuku M
    6. Ito M
    7. Nakano T
    8. Okawa K
    9. Iwamatsu A
    10. Kaibuchi K

    (1996) Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein rho

    The EMBO Journal 15:2208–2216.

    https://doi.org/10.1002/j.1460-2075.1996.tb00574.x

    • PubMed
    • Google Scholar
46. 1. Mayor R
    2. Etienne-Manneville S

    (2016) The front and rear of collective cell migration

    Nature Reviews Molecular Cell Biology 17:97–109.

    https://doi.org/10.1038/nrm.2015.14

    • PubMed
    • Google Scholar
47. 1. McDonald JA
    2. Pinheiro EM
    3. Kadlec L
    4. Schupbach T
    5. Montell DJ

    (2006) Multiple EGFR ligands participate in guiding migrating border cells

    Developmental Biology 296:94–103.

    https://doi.org/10.1016/j.ydbio.2006.04.438

    • PubMed
    • Google Scholar
48. 1. McEwen AE
    2. Maher MT
    3. Mo R
    4. Gottardi CJ

    (2014) E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion

    Molecular Biology of the Cell 25:2365–2374.

    https://doi.org/10.1091/mbc.e14-01-0690

    • PubMed
    • Google Scholar
49. 1. McGuire SE
    2. Mao Z
    3. Davis RL

    (2004) Spatiotemporal gene expression targeting with the TARGET and Gene-Switch systems in Drosophila

    Science Signaling 2004:pl6.

    https://doi.org/10.1126/stke.2202004pl6

    • Google Scholar
50. 1. Mège RM
    2. Ishiyama N

    (2017) Integration of cadherin adhesion and cytoskeleton at Adherens Junctions

    Cold Spring Harbor Perspectives in Biology 9:a028738.

    https://doi.org/10.1101/cshperspect.a028738

    • PubMed
    • Google Scholar
51. 1. Melani M
    2. Simpson KJ
    3. Brugge JS
    4. Montell D

    (2008) Regulation of cell adhesion and collective cell migration by Hindsight and its human homolog RREB1

    Current Biology 18:532–537.

    https://doi.org/10.1016/j.cub.2008.03.024

    • PubMed
    • Google Scholar
52. 1. Mishra AK
    2. Mondo JA
    3. Campanale JP
    4. Montell DJ

    (2019) Coordination of protrusion dynamics within and between collectively migrating border cells by myosin II

    Molecular Biology of the Cell 30:2490–2502.

    https://doi.org/10.1091/mbc.E19-02-0124

    • PubMed
    • Google Scholar
53. 1. Miskei M
    2. Ádám C
    3. Kovács L
    4. Karányi Z
    5. Dombrádi V

    (2011) Molecular evolution of phosphoprotein phosphatases in Drosophila

    PLOS ONE 6:e22218.

    https://doi.org/10.1371/journal.pone.0022218

    • PubMed
    • Google Scholar
54. 1. Mohr SE
    2. Smith JA
    3. Shamu CE
    4. Neumüller RA
    5. Perrimon N

    (2014) RNAi screening comes of age: improved techniques and complementary approaches

    Nature Reviews Molecular Cell Biology 15:591–600.

    https://doi.org/10.1038/nrm3860

    • PubMed
    • Google Scholar
55. 1. Montell DJ
    2. Rorth P
    3. Spradling AC

    (1992) Slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C/EBP

    Cell 71:51–62.

    https://doi.org/10.1016/0092-8674(92)90265-E

    • PubMed
    • Google Scholar
56. 1. Montell DJ
    2. Yoon WH
    3. Starz-Gaiano M

    (2012) Group choreography: mechanisms orchestrating the collective movement of border cells

    Nature Reviews Molecular Cell Biology 13:631–645.

    https://doi.org/10.1038/nrm3433

    • PubMed
    • Google Scholar
57. 1. Niewiadomska P
    2. Godt D
    3. Tepass U

    (1999) DE-Cadherin is required for intercellular motility during Drosophila oogenesis

    Journal of Cell Biology 144:533–547.

    https://doi.org/10.1083/jcb.144.3.533

    • PubMed
    • Google Scholar
58. 1. Oleinik NV
    2. Krupenko NI
    3. Krupenko SA

    (2010) ALDH1L1 inhibits cell motility via dephosphorylation of cofilin by PP1 and PP2A

    Oncogene 29:6233–6244.

    https://doi.org/10.1038/onc.2010.356

    • PubMed
    • Google Scholar
59. 1. Ong S
    2. Foote C
    3. Tan C

    (2010) Mutations of DMYPT cause over constriction of contractile rings and ring canals during Drosophila germline cyst formation

    Developmental Biology 346:161–169.

    https://doi.org/10.1016/j.ydbio.2010.06.008

    • PubMed
    • Google Scholar
60. 1. Pacquelet A
    2. Rørth P

    (2005) Regulatory mechanisms required for DE-cadherin function in cell migration and other types of adhesion

    Journal of Cell Biology 170:803–812.

    https://doi.org/10.1083/jcb.200506131

    • PubMed
    • Google Scholar
61. 1. Parker L
    2. Gross S
    3. Beullens M
    4. Bollen M
    5. Bennett D
    6. Alphey L

    (2002) Functional interaction between nuclear inhibitor of protein phosphatase type 1 (NIPP1) and protein phosphatase type 1 (PP1) in Drosophila: consequences of over-expression of NIPP1 in flies and suppression by co-expression of PP1

    Biochemical Journal 368:789–797.

    https://doi.org/10.1042/bj20020582

    • PubMed
    • Google Scholar
62. 1. Plutoni C
    2. Keil S
    3. Zeledon C
    4. Delsin LEA
    5. Decelle B
    6. Roux PP
    7. Carréno S
    8. Emery G

    (2019) Misshapen coordinates protrusion restriction and actomyosin contractility during collective cell migration

    Nature Communications 10:3940.

    https://doi.org/10.1038/s41467-019-11963-7

    • Google Scholar
63. 1. Poukkula M
    2. Cliffe A
    3. Changede R
    4. Rørth P

    (2011) Cell behaviors regulated by guidance cues in collective migration of border cells

    The Journal of Cell Biology 192:513–524.

    https://doi.org/10.1083/jcb.201010003

    • PubMed
    • Google Scholar
64. 1. Prasad M
    2. Montell DJ

    (2007) Cellular and molecular mechanisms of border cell migration analyzed using time-lapse live-cell imaging

    Developmental Cell 12:997–1005.

    https://doi.org/10.1016/j.devcel.2007.03.021

    • PubMed
    • Google Scholar
65. 1. Priya R
    2. Gomez GA
    3. Budnar S
    4. Verma S
    5. Cox HL
    6. Hamilton NA
    7. Yap AS

    (2015) Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions

    Nature Cell Biology 17:1282–1293.

    https://doi.org/10.1038/ncb3239

    • PubMed
    • Google Scholar
66. 1. Qin X
    2. Park BO
    3. Liu J
    4. Chen B
    5. Choesmel-Cadamuro V
    6. Belguise K
    7. Heo WD
    8. Wang X

    (2017) Cell-matrix adhesion and cell-cell adhesion differentially control basal myosin oscillation and Drosophila egg chamber elongation

    Nature Communications 8:14708.

    https://doi.org/10.1038/ncomms14708

    • PubMed
    • Google Scholar
67. 1. Ramel D
    2. Wang X
    3. Laflamme C
    4. Montell DJ
    5. Emery G

    (2013) Rab11 regulates cell-cell communication during collective cell movements

    Nature Cell Biology 15:317–324.

    https://doi.org/10.1038/ncb2681

    • PubMed
    • Google Scholar
68. 1. Ratheesh A
    2. Gomez GA
    3. Priya R
    4. Verma S
    5. Kovacs EM
    6. Jiang K
    7. Brown NH
    8. Akhmanova A
    9. Stehbens SJ
    10. Yap AS

    (2012) Centralspindlin and α-catenin regulate rho signalling at the epithelial zonula adherens

    Nature Cell Biology 14:818–828.

    https://doi.org/10.1038/ncb2532

    • PubMed
    • Google Scholar
69. 1. Raza Q
    2. Choi JY
    3. Li Y
    4. O'Dowd RM
    5. Watkins SC
    6. Chikina M
    7. Hong Y
    8. Clark NL
    9. Kwiatkowski AV

    (2019) Evolutionary rate covariation analysis of E-cadherin identifies raskol as a regulator of cell adhesion and actin dynamics in Drosophila

    PLOS Genetics 15:e1007720.

    https://doi.org/10.1371/journal.pgen.1007720

    • PubMed
    • Google Scholar
70. 1. Reffay M
    2. Parrini MC
    3. Cochet-Escartin O
    4. Ladoux B
    5. Buguin A
    6. Coscoy S
    7. Amblard F
    8. Camonis J
    9. Silberzan P

    (2014) Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells

    Nature Cell Biology 16:217–223.

    https://doi.org/10.1038/ncb2917

    • PubMed
    • Google Scholar
71. 1. Ridley AJ

    (2011) Life at the leading edge

    Cell 145:1012–1022.

    https://doi.org/10.1016/j.cell.2011.06.010

    • PubMed
    • Google Scholar
72. 1. Rørth P
    2. Szabo K
    3. Bailey A
    4. Laverty T
    5. Rehm J
    6. Rubin GM
    7. Weigmann K
    8. Milán M
    9. Benes V
    10. Ansorge W
    11. Cohen SM

    (1998)

    Systematic gain-of-function genetics in Drosophila

    Development 125:1049–1057.

    • PubMed
    • Google Scholar
73. 1. Saadin A
    2. Starz-Gaiano M

    (2016) Circuitous genetic regulation governs a straightforward cell migration

    Trends in Genetics 32:660–673.

    https://doi.org/10.1016/j.tig.2016.08.001

    • PubMed
    • Google Scholar
74. 1. Sarov M
    2. Barz C
    3. Jambor H
    4. Hein MY
    5. Schmied C
    6. Suchold D
    7. Stender B
    8. Janosch S
    9. Kj VV
    10. Krishnan RT
    11. Krishnamoorthy A
    12. Ferreira IR
    13. Ejsmont RK
    14. Finkl K
    15. Hasse S
    16. Kämpfer P
    17. Plewka N
    18. Vinis E
    19. Schloissnig S
    20. Knust E
    21. Hartenstein V
    22. Mann M
    23. Ramaswami M
    24. VijayRaghavan K
    25. Tomancak P
    26. Schnorrer F

    (2016) A genome-wide resource for the analysis of protein localisation in Drosophila

    eLife 5:e12068.

    https://doi.org/10.7554/eLife.12068

    • PubMed
    • Google Scholar
75. 1. Sarpal R
    2. Pellikka M
    3. Patel RR
    4. Hui FY
    5. Godt D
    6. Tepass U

    (2012) Mutational analysis supports a core role for Drosophila α-catenin in adherens junction function

    Journal of Cell Science 125:233–245.

    https://doi.org/10.1242/jcs.096644

    • PubMed
    • Google Scholar
76. 1. Sawant K
    2. Chen Y
    3. Kotian N
    4. Preuss KM
    5. McDonald JA

    (2018) Rap1 GTPase promotes coordinated collective cell migration in vivo

    Molecular Biology of the Cell 29:2656–2673.

    https://doi.org/10.1091/mbc.E17-12-0752

    • PubMed
    • Google Scholar
77. 1. Scarpa E
    2. Mayor R

    (2016) Collective cell migration in development

    Journal of Cell Biology 212:143–155.

    https://doi.org/10.1083/jcb.201508047

    • PubMed
    • Google Scholar
78. 1. Schindelin J
    2. Arganda-Carreras I
    3. Frise E
    4. Kaynig V
    5. Longair M
    6. Pietzsch T
    7. Preibisch S
    8. Rueden C
    9. Saalfeld S
    10. Schmid B
    11. Tinevez JY
    12. White DJ
    13. Hartenstein V
    14. Eliceiri K
    15. Tomancak P
    16. Cardona A

    (2012) Fiji: an open-source platform for biological-image analysis

    Nature Methods 9:676–682.

    https://doi.org/10.1038/nmeth.2019

    • PubMed
    • Google Scholar
79. 1. Shellard A
    2. Szabó A
    3. Trepat X
    4. Mayor R

    (2018) Supracellular contraction at the rear of neural crest cell groups drives collective chemotaxis

    Science 362:339–343.

    https://doi.org/10.1126/science.aau3301

    • PubMed
    • Google Scholar
80. 1. Shellard A
    2. Mayor R

    (2019) Supracellular migration - beyond collective cell migration

    Journal of Cell Science 132:jcs226142.

    https://doi.org/10.1242/jcs.226142

    • PubMed
    • Google Scholar
81. 1. Silver DL
    2. Montell DJ

    (2001) Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila

    Cell 107:831–841.

    https://doi.org/10.1016/S0092-8674(01)00607-9

    • PubMed
    • Google Scholar
82. 1. Spracklen AJ
    2. Kelpsch DJ
    3. Chen X
    4. Spracklen CN
    5. Tootle TL

    (2014) Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis

    Molecular Biology of the Cell 25:397–411.

    https://doi.org/10.1091/mbc.e13-07-0366

    • PubMed
    • Google Scholar
83. 1. Stappert J
    2. Kemler R

    (1994) A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated

    Cell Adhesion and Communication 2:319–327.

    https://doi.org/10.3109/15419069409014207

    • PubMed
    • Google Scholar
84. 1. Starz-Gaiano M
    2. Melani M
    3. Wang X
    4. Meinhardt H
    5. Montell DJ

    (2008) Feedback inhibition of jak/STAT signaling by apontic is required to limit an invasive cell population

    Developmental Cell 14:726–738.

    https://doi.org/10.1016/j.devcel.2008.03.005

    • PubMed
    • Google Scholar
85. 1. Sun Y
    2. Yan Y
    3. Denef N
    4. Schüpbach T

    (2011) Regulation of somatic myosin activity by protein phosphatase 1β controls Drosophila oocyte polarization

    Development 138:1991–2001.

    https://doi.org/10.1242/dev.062190

    • PubMed
    • Google Scholar
86. 1. Te Boekhorst V
    2. Preziosi L
    3. Friedl P

    (2016) Plasticity of cell migration in vivo and in silico

    Annual Review of Cell and Developmental Biology 32:491–526.

    https://doi.org/10.1146/annurev-cellbio-111315-125201

    • PubMed
    • Google Scholar
87. 1. Tootle TL
    2. Spradling AC

    (2008) Drosophila pxt: a cyclooxygenase-like facilitator of follicle maturation

    Development 135:839–847.

    https://doi.org/10.1242/dev.017590

    • PubMed
    • Google Scholar
88. 1. Trinkle-Mulcahy L
    2. Sleeman JE
    3. Lamond AI

    (2001)

    Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells

    Journal of Cell Science 114:4219–4228.

    • PubMed
    • Google Scholar
89. 1. Van Eynde A
    2. Wera S
    3. Beullens M
    4. Torrekens S
    5. Van Leuven F
    6. Stalmans W
    7. Bollen M

    (1995) Molecular cloning of NIPP-1, a nuclear inhibitor of protein Phosphatase-1, reveals homology with polypeptides involved in RNA processing

    The Journal of Biological Chemistry 270:28068–28074.

    https://doi.org/10.1074/jbc.270.47.28068

    • PubMed
    • Google Scholar
90. 1. Verbinnen I
    2. Ferreira M
    3. Bollen M

    (2017) Biogenesis and activity regulation of protein phosphatase 1

    Biochemical Society Transactions 45:89–99.

    https://doi.org/10.1042/BST20160154

    • PubMed
    • Google Scholar
91. 1. Vicente-Manzanares M
    2. Ma X
    3. Adelstein RS
    4. Horwitz AR

    (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration

    Nature Reviews Molecular Cell Biology 10:778–790.

    https://doi.org/10.1038/nrm2786

    • PubMed
    • Google Scholar
92. 1. Wang X
    2. He L
    3. Wu YI
    4. Hahn KM
    5. Montell DJ

    (2010) Light-mediated activation reveals a key role for rac in collective guidance of cell movement in vivo

    Nature Cell Biology 12:591–597.

    https://doi.org/10.1038/ncb2061

    • PubMed
    • Google Scholar
93. 1. Wang X
    2. Enomoto A
    3. Asai N
    4. Kato T
    5. Takahashi M

    (2016) Collective invasion of Cancer: perspectives from pathology and development

    Pathology International 66:183–192.

    https://doi.org/10.1111/pin.12391

    • PubMed
    • Google Scholar
94. 1. Wang H
    2. Qiu Z
    3. Xu Z
    4. Chen SJ
    5. Luo J
    6. Wang X
    7. Chen J

    (2018) aPKC is a key polarity determinant in coordinating the function of three distinct cell polarities during collective migration

    Development 145:dev158444.

    https://doi.org/10.1242/dev.158444

    • PubMed
    • Google Scholar
95. 1. Weiser DC
    2. Row RH
    3. Kimelman D

    (2009) Rho-regulated myosin phosphatase establishes the level of protrusive activity required for cell movements during zebrafish gastrulation

    Development 136:2375–2384.

    https://doi.org/10.1242/dev.034892

    • PubMed
    • Google Scholar
96. 1. Winkler C
    2. De Munter S
    3. Van Dessel N
    4. Lesage B
    5. Heroes E
    6. Boens S
    7. Beullens M
    8. Van Eynde A
    9. Bollen M

    (2015) The selective inhibition of protein phosphatase-1 results in mitotic catastrophe and impaired tumor growth

    Journal of Cell Science 128:4526–4537.

    https://doi.org/10.1242/jcs.175588

    • PubMed
    • Google Scholar
97. 1. Xu T
    2. Rubin GM

    (1993)

    Analysis of genetic mosaics in developing and adult Drosophila tissues

    Development 117:1223–1237.

    • PubMed
    • Google Scholar
98. 1. Yamamoto S
    2. Bayat V
    3. Bellen HJ
    4. Tan C

    (2013) Protein phosphatase 1ß limits ring canal constriction during Drosophila germline cyst formation

    PLOS ONE 8:e70502.

    https://doi.org/10.1371/journal.pone.0070502

    • PubMed
    • Google Scholar
99. 1. Yap AS
    2. Duszyc K
    3. Viasnoff V

    (2018) Mechanosensing and mechanotransduction at cell-cell junctions

    Cold Spring Harbor Perspectives in Biology 10:a028761.

    https://doi.org/10.1101/cshperspect.a028761

    • PubMed
    • Google Scholar
100. 1. Zeledon C
     2. Sun X
     3. Plutoni C
     4. Emery G

     (2019) The ArfGAP drongo promotes actomyosin contractility during collective cell migration by releasing myosin phosphatase from the trailing edge

     Cell Reports 28:3238–3248.

     https://doi.org/10.1016/j.celrep.2019.08.044

     • PubMed
     • Google Scholar
101. 1. Zhang L
     2. Luo J
     3. Wan P
     4. Wu J
     5. Laski F
     6. Chen J

     (2011) Regulation of cofilin phosphorylation and asymmetry in collective cell migration during morphogenesis

     Development 138:455–464.

     https://doi.org/10.1242/dev.046870

     • PubMed
     • Google Scholar
102. 1. Zhang Y
     2. Kim TH
     3. Niswander L

     (2012) Phactr4 regulates directional migration of enteric neural crest through PP1, integrin signaling, and cofilin activity

     Genes & Development 26:69–81.

     https://doi.org/10.1101/gad.179283.111

     • PubMed
     • Google Scholar

Author details

1. Yujun Chen

   Division of Biology, Kansas State University, Manhattan, United States

   Contribution

   Conceptualization, Formal analysis, Funding acquisition, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-3190-6713

2. Nirupama Kotian

   Division of Biology, Kansas State University, Manhattan, United States

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

3. George Aranjuez

   Lerner Research Institute, Cleveland Clinic, Cleveland, United States

   Present address

   Division of Immunity and Pathogenesis, Burnett School of Biomedical, Sciences, University of Central Florida College of Medicine, Orlando, United States

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

4. Lin Chen

   LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

5. C Luke Messer

   Division of Biology, Kansas State University, Manhattan, United States

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

6. Ashley Burtscher

   Lerner Research Institute, Cleveland Clinic, Cleveland, United States

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

7. Ketki Sawant

   Division of Biology, Kansas State University, Manhattan, United States

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

8. Damien Ramel

   LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France

   Present address

   Institute of Metabolic and Cardiovascular Diseases (I2MC), Université de Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1048, Toulouse, France

   Contribution

   Conceptualization, Formal analysis, Validation, Investigation, Visualization, Methodology

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-9089-1497

9. Xiaobo Wang

   LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France

   Contribution

   Conceptualization, Resources, Formal analysis, Supervision, Funding acquisition

   Competing interests

   No competing interests declared

10. Jocelyn A McDonald

    Division of Biology, Kansas State University, Manhattan, United States

    Contribution

    Conceptualization, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology

    For correspondence

    jmcdona@ksu.edu

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-7494-1466

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