Spatiotemporal Features of Early Neuronogenesis Differ in Wild-Type and Albino Mouse Retina

Abstract

In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

Rewiring the retinal ganglion cell gene regulatory network: Neurod1 promotes retinal ganglion cell fate in the absence of Math5

“…In Math5 lacZ-KI/+ (wild-type) retinas, Pou4f2 and Isl1 were co-expressed in differentiating RGCs, as we and others have shown previously (Fig. 4A,A1,A2) (Rachel et al, 2002;. Expression was largely absent in Math5 lacZ-KI/lacZ-KI retinas (Fig.…”

Navigating Neocortical Neurogenesis and Neuronal Specification: A Positional Information System Encoded by Neurogenetic Gradients

“…The time taken to generate corresponding laminar neuron classes as a proportion of the total neurogenetic interval is uniformly scaled across a wide range of species from rodents to primates . Moreover, variations in T G1 and/or gradients of transcription factors are known to be characteristic of the proliferative epithelium in other regions of the developing CNS [e.g., the retina (Alexiades and Cepko, 1996;O'Leary and Nakagawa, 2002;Rachel et al, 2002;Schuurmans and Guillemot, 2002;Grove and Fukuchi-Shimogori, 2003)]. Thus, it is plausible that the ability of PVE cells to know their position by monitoring simultaneously T G1 and gradient expressions of molecules and then to coordinate this positional information with transcriptional mechanisms related to specification of cell fates and numbers is a general feature of the developing CNS.…”

Foxd1 is required for proper formation of the optic chiasm

“…Anterograde labeling of the whole retinal projection with DiI, and retrograde tracing using rhodamine-dextran applied to the optic tract, were performed as described (Erskine et al, 2000;Herrera et al, 2003;Rachel et al, 2002).…”