Valdivia, LE;
Lamb, DB;
Horner, W;
Wierzbicki, C;
Tafessu, A;
Williams, AM;
Gestri, G;
Krasnow, AM;
Vleeshouwer-Neumann, TS;
Givens, M;
et al.
Valdivia, LE; Lamb, DB; Horner, W; Wierzbicki, C; Tafessu, A; Williams, AM; Gestri, G; Krasnow, AM; Vleeshouwer-Neumann, TS; Givens, M; Young, RM; Lawrence, LM; Stickney, HL; Hawkins, TA; Schwarz, QP; Cavodeassi, F; Wilson, SW; Cerveny, KL
(2016)
Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish.
Development, 143 (7).
pp. 1087-1098.
ISSN 1477-9129
https://doi.org/10.1242/dev.130922
SGUL Authors: Cavodeassi, Florencia
Abstract
Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye.
Item Type: |
Article
|
Additional Information: |
© 2016. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: |
BMP, Ciliary marginal zone, Gdf6a, Neurogenesis, Retinal stem cells, Retinoic acid, Zebrafish, Animals, Bone Morphogenetic Proteins, Cell Cycle, Cell Proliferation, Embryo, Nonmammalian, Growth Differentiation Factor 6, Neurogenesis, Retina, Signal Transduction, Stem Cells, Tretinoin, Zebrafish, Zebrafish Proteins, 06 Biological Sciences, 11 Medical And Health Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Institute of Medical & Biomedical Education (IMBE) Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE) |
Journal or Publication Title: |
Development |
ISSN: |
1477-9129 |
Language: |
eng |
Dates: |
Date | Event |
---|
5 April 2016 | Published | 18 February 2016 | Published Online | 8 February 2016 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 3.0 |
Projects: |
|
PubMed ID: |
26893342 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/109998 |
Publisher's version: |
https://doi.org/10.1242/dev.130922 |
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