RRC ID 49678
Author 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.
Title Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish.
Journal Development
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.
Volume 143(7)
Pages 1087-98
Published 2016-4-1
DOI 10.1242/dev.130922
PII dev.130922
PMID 26893342
PMC PMC4852494
MeSH Animals Bone Morphogenetic Proteins / metabolism Cell Cycle / genetics Cell Proliferation Embryo, Nonmammalian / embryology Growth Differentiation Factor 6 / genetics* Neurogenesis / genetics* Neurogenesis / physiology Retina / embryology* Signal Transduction / genetics Stem Cells / cytology Tretinoin / metabolism* Zebrafish / embryology* Zebrafish Proteins / genetics*
IF 5.611
Times Cited 13
Zebrafish Tg(chx10:GFP)