POU domain factor Brn-3b is essential for retinal ganglion cell differentiation and survival but not for initial cell fate specification

While the mammalian retina is well understood at the anatomical and physiol ogical levels, little is known about the mechanisms that give rise to the r etina's highly ordered pattern or its diverse neuronal cell types. Previous investigations have shown that gene disruption of the POU-IV class transcr iption factor Brn-3b (Brn-3.2) resulted in the loss of most retinal ganglio n cells in retinas of postnatal mice. Here, we used lacZ and human placenta l alkaline phosphatase genes knocked into the brn-3b locus to follow the fa te of brn-3b-mutant cells in the developing retina. We found that Brn-3b wa s not required for the initial commitment of retinal ganglion cell fate or for the migration of ganglion cells to the ganglion cell layer. However, Br n-3b was essential for the normal differentiation of retinal ganglion cells ; without it, the cells underwent enhanced apoptosis. Retinal ganglion cell s lacking brn-3b extended processes at the appropriate time in development, but these processes were disorganized, resulting in a thinner optic nerve. Explanted retinas from brn-3b-null embryos also extended processes when cu ltured in vitro, but the processes were shorter and less bundled than in wi ld-type retinas. Ultrastructural and marker analyses showed that the proces ses of mutant ganglion cells had dendritic rather than axonal features, sug gesting that mutant cells formed dendrites in place of axons. These results suggest that Brn-3b regulates the activity of genes whose products play es sential roles in the formation of retinal ganglion cell axons. (C) 1999 Aca demic Press.