Cell birthdays and rate of differentiation of ganglion and horizontal cells of the developing cat's retina.

Tritiated thymidine autoradiography experiments demonstrated that three cell classes are produced by ventricular cells during the first phase of neurogenesis: retinal ganglion cells, A-type horizontal cells, and cone photoreceptors. Light microscopy and scanning electron microscopy were used to study the migration and morphological differentiation of these three cell classes. The patterns of postmitotic migration are of interest because these three classes of cells are found in three different layers of the adult retina. Cones retain their position at the outer limiting membrane (OLM) throughout life and do not migrate. Ganglion cells migrate immediately to the proximal (vitread) layer of the retina and begin to differentiate. In contrast, A-type horizontal cells migrated away from the OLM within 10-14 days after their final mitosis but were morphologically relatively undifferentiated at that time. Subsequent differentiation of the A-type horizontal cell is also protracted; dendrites are not observed until approximately 3 weeks after the final mitosis. These observations suggest that there are several interacting mechanisms involved in neurogenesis: a sequence that produces a specific cohort of committed cells at a specific time, the subsequent migration of postmitotic neuroblasts to an appropriate position in the retina, and a spatial gradient of differentiation increasing from distal to proximal layers. While this distribution of differentiated cells early in fetal development is striking, the existence of underlying time-dependent processes that might cause this apparent spatial phenomenon cannot be eliminated.