Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism
Abstract
The developmental strategies used by progenitor cells to allow a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a mechanism of progenitor cell allocation that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the superficial epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-lasting apical contacts that enable the epithelial layer to pull a subset of progenitors on their way to the vegetal pole. The remaining delaminated cells follow the movement of apically attached progenitors by a protrusion-dependent cell-cell contact mechanism, avoiding sequestration by the adjacent endoderm, ensuring their collective fate and allocation at the site of differentiation. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7 and 8.
Article and author information
Author details
Funding
Fondo Nacional de Desarrollo Científico y Tecnológico (1190806)
- Eduardo Pulgar
- Steffen Härtel
- Miguel Concha
Comisión Nacional de Investigación Científica y Tecnológica (REDES170212,REDES130020)
- Eduardo Pulgar
- Steffen Härtel
- Miguel Concha
H2020 European Research Council (Advanced grant 742573)
- Carl-Philipp Heisenberg
Fondo Nacional de Desarrollo Científico y Tecnológico (1161274,1181823)
- Steffen Härtel
- Miguel Concha
Instituto Milenio de Neurociencia Biomedica (ICN09_015)
- Eduardo Pulgar
- Steffen Härtel
- Miguel Concha
Millennium Nucleus Physics of Active Matter from ANID (ANID)
- Susana Márquez
- Rodrigo Soto
- Miguel Concha
Fondo de Equipamiento Cientifico y Tecnologico (EQM130051)
- Steffen Härtel
- Miguel Concha
Fondo de Financiamiento de Centros de Investigacion en Areas Prioritarias (15150012)
- Miguel Concha
Fondo Nacional de Desarrollo Científico y Tecnológico (3160478)
- Eduardo Pulgar
Comisión Nacional de Investigación Científica y Tecnológica (PIA ACT-1402)
- Steffen Härtel
- Miguel Concha
Comisión Nacional de Investigación Científica y Tecnológica (PIA ACT192015)
- Miguel Concha
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Julien Vermot
Ethics
Animal experimentation: Fish care and procedures were approved by the Ethical Review Committee and comply with the Animals Scientific Procedures Act 0466 (Protocol CBA#0466 FMUCH).
Version history
- Received: January 12, 2021
- Preprint posted: April 29, 2021 (view preprint)
- Accepted: August 25, 2021
- Accepted Manuscript published: August 27, 2021 (version 1)
- Version of Record published: September 23, 2021 (version 2)
- Version of Record updated: November 23, 2021 (version 3)
Copyright
© 2021, Pulgar 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
-
- 1,170
- Page views
-
- 184
- Downloads
-
- 4
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
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)
Further reading
-
- Developmental Biology
- Immunology and Inflammation
During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.
-
- Developmental Biology
- Neuroscience
Autism spectrum disorder (ASD) is defined by common behavioral characteristics, raising the possibility of shared pathogenic mechanisms. Yet, vast clinical and etiological heterogeneity suggests personalized phenotypes. Surprisingly, our iPSC studies find that six individuals from two distinct ASD subtypes, idiopathic and 16p11.2 deletion, have common reductions in neural precursor cell (NPC) neurite outgrowth and migration even though whole genome sequencing demonstrates no genetic overlap between the datasets. To identify signaling differences that may contribute to these developmental defects, an unbiased phospho-(p)-proteome screen was performed. Surprisingly despite the genetic heterogeneity, hundreds of shared p-peptides were identified between autism subtypes including the mTOR pathway. mTOR signaling alterations were confirmed in all NPCs across both ASD subtypes, and mTOR modulation rescued ASD phenotypes and reproduced autism NPC-associated phenotypes in control NPCs. Thus, our studies demonstrate that genetically distinct ASD subtypes have common defects in neurite outgrowth and migration which are driven by the shared pathogenic mechanism of mTOR signaling dysregulation.