Neurog2 controls the leading edge of neurogenesis in the mammalian retina.
In the mammalian retina, neuronal differentiation begins in the dorso-central optic cup and sweeps peripherally and ventrally. While certain extrinsic factors have been implicated, little is known about the intrinsic factors that direct this process. In this study, we evaluate the expression and function of proneural bHLH transcription factors during the onset of mouse retinal neurogenesis. Dorso-central retinal progenitor cells that give rise to the first postmitotic neurons express Neurog2/Ngn2 and Atoh7/Math5. In the absence of Neurog2, the spread of neurogenesis stalls, along with Atoh7 expression and RGC differentiation. However, neurogenesis is eventually restored, and at birth Neurog2 mutant retinas are reduced in size, with only a slight increase in the retinal ganglion cell population. We find that the re-establishment of neurogenesis coincides with the onset of Ascl1 expression, and that Ascl1 can rescue the early arrest of neural development in the absence of Neurog2. Together, this study supports the hypothesis that the intrinsic factors Neurog2 and Ascl1 regulate the temporal progression of retinal neurogenesis by directing overlapping waves of neuron formation.
Departments of Pediatrics and Ophthalmology, Division of Developmental Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Robert B
RB
Hufnagel
Tien T
TT
Le
Ashley L
AL
Riesenberg
Nadean L
NL
Brown
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis; D012160:Retina / Q000196:embryology / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D001616:beta-Galactosidase; C102938:Neurog2 protein, mouse