Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina

  1. Rana Amini
  2. Archit Bhatnagar
  3. Raimund Schlüßler
  4. Stephanie Möllmert
  5. Jochen Guck
  6. Caren Norden  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Technische Universität Dresden, Germany
  3. Max Planck Institute for the Science of Light, Germany

Abstract

Migration of cells in the developing brain is integral for the establishment of neural circuits and function of the central nervous system. While migration modes during which neurons employ predetermined directional guidance of either preexisting neuronal processes or underlying cells have been well explored, less is known about how cells featuring multipolar morphology migrate in the dense environment of the developing brain. To address this, we here investigated multipolar migration of horizontal cells in the zebrafish retina. We found that these cells feature several hallmarks of amoeboid-like migration that enable them to tailor their movements to the spatial constraints of the crowded retina. These hallmarks include cell and nuclear shape changes, as well as persistent rearward polarization of stable F-actin. Interference with the organization of the developing retina by changing nuclear properties or overall tissue architecture, hampers efficient horizontal cell migration and layer formation showing that cell-tissue interplay is crucial for this process. In view of the high proportion of multipolar migration phenomena observed in brain development, the here uncovered ameboid-like migration mode might be conserved in other areas of the developing nervous system.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided

Article and author information

Author details

  1. Rana Amini

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3974-5072
  2. Archit Bhatnagar

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Raimund Schlüßler

    Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3752-2382
  4. Stephanie Möllmert

    Max Planck Institute for the Science of Light, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Jochen Guck

    Max Planck Institute for the Science of Light, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Caren Norden

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    cnorden@igc.gulbenkian.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8835-1451

Funding

H2020 European Research Council (ERC-2018-CoG-81904)

  • Caren Norden

Natural Sciences and Engineering Research Council of Canada (502961)

  • Rana Amini

Fonds de Recherche du Québec - Santé (35510)

  • Rana Amini

Max Planck Institute of Molecular Cell Biology and Genetics (open access funding)

  • Rana Amini

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal work was performed in accordance with the European Union (EU) directive 2010/63/EU, as well as the German Animal Welfare act.

Copyright

© 2022, Amini et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,776
    views
  • 407
    downloads
  • 15
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rana Amini
  2. Archit Bhatnagar
  3. Raimund Schlüßler
  4. Stephanie Möllmert
  5. Jochen Guck
  6. Caren Norden
(2022)
Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina
eLife 11:e76408.
https://doi.org/10.7554/eLife.76408

Share this article

https://doi.org/10.7554/eLife.76408

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Thi Thom Mac, Teddy Fauquier ... Thierry Brue
    Research Article

    Deficient Anterior pituitary with common Variable Immune Deficiency (DAVID) syndrome results from NFKB2 heterozygous mutations, causing adrenocorticotropic hormone deficiency (ACTHD) and primary hypogammaglobulinemia. While NFKB signaling plays a crucial role in the immune system, its connection to endocrine symptoms is unclear. We established a human disease model to investigate the role of NFKB2 in pituitary development by creating pituitary organoids from CRISPR/Cas9-edited human induced pluripotent stem cells (hiPSCs). Introducing homozygous TBX19K146R/K146R missense pathogenic variant in hiPSC, an allele found in congenital isolated ACTHD, led to a strong reduction of corticotrophs number in pituitary organoids. Then, we characterized the development of organoids harboring NFKB2D865G/D865G mutations found in DAVID patients. NFKB2D865G/D865G mutation acted at different levels of development with mutant organoids displaying changes in the expression of genes involved on pituitary progenitor generation (HESX1, PITX1, LHX3), hypothalamic secreted factors (BMP4, FGF8, FGF10), epithelial-to-mesenchymal transition, lineage precursors development (TBX19, POU1F1) and corticotrophs terminal differentiation (PCSK1, POMC), and showed drastic reduction in the number of corticotrophs. Our results provide strong evidence for the direct role of NFKB2 mutations in the endocrine phenotype observed in patients leading to a new classification of a NFKB2 variant of previously unknown clinical significance as pathogenic in pituitary development.

    1. Developmental Biology
    2. Genetics and Genomics
    Debashish U Menon, Prabuddha Chakraborty ... Terry Magnuson
    Research Article

    We present evidence implicating the BAF (BRG1/BRM Associated Factor) chromatin remodeler in meiotic sex chromosome inactivation (MSCI). By immunofluorescence (IF), the putative BAF DNA binding subunit, ARID1A (AT-rich Interaction Domain 1 a), appeared enriched on the male sex chromosomes during diplonema of meiosis I. Germ cells showing a Cre-induced loss of ARID1A arrested in pachynema and failed to repress sex-linked genes, indicating a defective MSCI. Mutant sex chromosomes displayed an abnormal presence of elongating RNA polymerase II coupled with an overall increase in chromatin accessibility detectable by ATAC-seq. We identified a role for ARID1A in promoting the preferential enrichment of the histone variant, H3.3, on the sex chromosomes, a known hallmark of MSCI. Without ARID1A, the sex chromosomes appeared depleted of H3.3 at levels resembling autosomes. Higher resolution analyses by CUT&RUN revealed shifts in sex-linked H3.3 associations from discrete intergenic sites and broader gene-body domains to promoters in response to the loss of ARID1A. Several sex-linked sites displayed ectopic H3.3 occupancy that did not co-localize with DMC1 (DNA meiotic recombinase 1). This observation suggests a requirement for ARID1A in DMC1 localization to the asynapsed sex chromatids. We conclude that ARID1A-directed H3.3 localization influences meiotic sex chromosome gene regulation and DNA repair.