Abnormal polarization and axon outgrowth in retinal ganglion cells lackingthe POU-domain transcription factor Brn-3b

The POU domain transcription factor Brn-3b (also called Brn-3.2) is essenti al for the normal development of retinal ganglion cells (RGCs) in the mouse . Without Brn-3b, RGCs commit to their fate and migrate to the ganglion cel l layer, but most cells die during fetal development. An earlier report (L. can ef al., 1999, Dev. Biol. 210, 469-480) suggested that cell death was c aused by abnormal axon formation. Here, we use retinal explants from wild-t ype and mutant embryos to show that bm-3b-deficient RGCs are not properly p olarized and tend to form dendrites rather than axons. Compared with wild-t ype explants, neurites of RGCs from bm-3b-deficient retinal explants grew s lower, were shorter, and did not fasciculate properly. Mutant neurites had more microtubules than wildtype controls, and the arrangement of microtubul es and neurofilaments was characteristic of dendrites rather than axons. Ne urites from individual mutant RGCs displayed abnormal polarity and had dend rite-like branches extending outward from their main axis. Most mutant RGCs exhibited abnormal migratory behavior, and their neurites labeled intensel y with the dendrite marker MAP-2. A small number of mutant RGCs were not mi gratory, and their neurites were longer and labeled positively for the axon marker tau-l, suggesting that some RGCs were not as severely affected by t he absence of Brn-3b as others. Although tau-l was not observed in most mut ant neurites, it did accumulate in mutant cell bodies, implying that the ab sence of Brn-3b caused a defect in axon transport. Thus, Brn-3b appears to control the activity of genes that function in establishing RGC polarity, a nd without Brn-3b, RGCs cannot extend normal axons.