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The Journal of Neuroscience, June 1, 2002, 22(11):4249-4263

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

Rivka A. Rachel¹, Gül Dölen², Nancy L. Hayes⁴, Alice Lu², Lynda Erskine², Richard S. Nowakowski⁴, and Carol A. Mason^{1, 2, 3}

¹ Center for Neurobiology and Behavior, ² Department of Pathology, and ³ Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, and ⁴ Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

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.

Key words: albino; biotinylated dextran amine; bromodeoxyuridine; cell cycle; flow cytometry; Islet1/2; melanin; neuronogenesis; neurogenesis; phenylthiourea; retinal ganglion cell; retinal pigment epithelium; thymidine; ventricular zone

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22114249-15$05.00/0

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