REQUIREMENT FOR BRN-3B IN EARLY DIFFERENTIATION OF POSTMITOTIC RETINAL GANGLION-CELL PRECURSORS

The Brn-3 subfamily of POU domain transcription factors consists of Br n-3a, -3b, and -3c, which are important regulators for sensorineural d evelopment, Despite the expression of all three factors in retinal gan glion cells, earlier studies have shown that Brn-3b is the only one am ong the three Brn-3 genes that is essential for development of similar to 70% of ganglion cells in the murine retina. I report here that Brn -3b displays a spatiotemporal expression pattern characteristic of the dynamic profile of ganglion cell genesis during murine retinal develo pment. Moreover, it is initially turned on in postmitotic ganglion cel l precursors 2 days before the onset of Brn-3a and -3c expression in d ifferentiated ganglion cells. During the entire period of retinal gang lion cell genesis, the postmitotic ganglion cell precursors that would normally become Brn-3b(+) cells fail to properly differentiate in Bm- 3b(-/-) mice, as evidenced by a twofold reduction in the optic nerve s ize and diminished expression of several ganglion cell markers. The un differentiated ganglion cell precursors appear to be degenerated by ap optosis within the ganglion cell layer during the perinatal and early postnatal period. I propose that retinal ganglion cells develop follow ing two separate differentiation pathways-Brn-3b dependent and Brn-3b independent. In the Brn-3b-dependent mechanism, Brn-3b may be required to initiate a particular differentiation program for a large set of p ostmitotic ganglion precursors to properly differentiate into the 70%, Brn-3b-dependent retinal ganglion cells. (C) 1998 Academic Press.