Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina.
The timing of cell cycle exit and temporal changes in the developmental competence of precursor cells are key components for the establishment of the normal complement of cell types in the mammalian retina. The identity of cell extrinsic cues that control these processes is largely unknown. We showed previously in mouse retina that sonic hedgehog (Shh) signalling from retinal ganglion cells (RGCs) to retinal precursor cells (RPC) is required for the establishment of normal retinal organization. Here, we show that conditional ablation of Shh expression in the peripheral mouse results in a depletion of the RPC pool, owing to precocious cell-cycle exit and neuronal differentiation. These changes were correlated with the downregulation of cyclin D1 and Hes1 gene expression. Shh inactivation also results in an increase in RGC number owing to a bias of RPC towards RGC production. In contrast to zebrafish, where Shh signalling drives cell cycle exit and RGC development, our findings indicate that in the mouse retina Shh signalling is required to maintain RPC proliferation and to control the timing of RGC development.
Wang
Yaping
Y
Molecular Medicine Program, Ottawa Health Research Institute and University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.
Dakubo
Gabriel D
GD
Thurig
Sherry
S
Mazerolle
Chantal J
CJ
Wallace
Valerie A
VA
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D015536:Down-Regulation; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D019426:Integrases; D015534:Trans-Activators; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C465570:Shh protein, mouse; C045073:Cre recombinase