title: 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.
authors.affiliation: Center for Neurobiology and Behavior, Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. rrachel@ncifcrf.gov
authors.forename: Rivka A
authors.initials: RA
authors.lastname: Rachel
authors.forename: Gul
authors.initials: G
authors.lastname: Dolen
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Hayes
authors.forename: Alice
authors.initials: A
authors.lastname: Lu
authors.forename: Lynda
authors.initials: L
authors.lastname: Erskine
authors.forename: Richard S
authors.initials: RS
authors.lastname: Nowakowski
authors.forename: Carol A
authors.initials: CA
authors.lastname: Mason
mesh_terms: D000417:Albinism / Q000196:embryology* / Q000473:pathology; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives*; D001973:Bromodeoxyuridine; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation; D002455:Cell Division; D003911:Dextrans; D005136:Eye Proteins / Q000096:biosynthesis; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D060850:LIM-Homeodomain Proteins; D008543:Melanins / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014442:Monophenol Monooxygenase / Q000172:deficiency; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology* / Q000473:pathology; D012160:Retina / Q000166:cytology* / Q000196:embryology* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000473:pathology; D016196:S Phase / Q000502:physiology; D013045:Species Specificity; D014157:Transcription Factors
chemical_list: D003911:Dextrans; D005136:Eye Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D008543:Melanins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C076397:biotinylated dextran amine; C063843:insulin gene enhancer binding protein Isl-1; D001710:Biotin; D014442:Monophenol Monooxygenase; D001973:Bromodeoxyuridine