The bHLH factors Xath5 and XNeuroD can upregulate the expression of XBrn3d, a POU-homeodomain transcription factor

The basic helix-loop-helix (bHLH) factor Xath5 promotes retinal ganglion ce ll differentiation when overexpressed and may do so by regulating the expre ssion of factors involved in the differentiation of these cells. Potential candidates include the Brn3 POU-homeodomain transcription factors, which ha ve been implicated in retinal ganglion cell development. Here we have ident ified a new member of the Brn3 gene subfamily in Xenopus, XBrn3d. In situ h ybridization analysis shows XBrn3d expression in developing sensory neurons and developing ganglion cells of the retina. Using a hormone-inducible Xat h5 fusion protein, we have shown that in animal caps Xath5 can directly reg ulate the expression of XBrn3d. Since XBrn3d is also expressed in sensory p opulations where Xath5 is not expressed, we examined the regulation of XBrn 3d expression by the bHLH factor XNeuroD. A XNeuroD-hGR fusion protein is s imilarly able to directly induce the expression of XBrn3d in animal caps. I n addition, overexpression of XBrn3d by RNA injection promotes the expressi on of ectopic sensory neuronal markers in the lateral ectoderm, suggesting a role in regulating neuronal development. Therefore, Xath5 and XNeuroD can directly regulate the expression of a neuronal subtype-specific factor, pr oviding a link between neuronal differentiation and cell fate specification . (C) 2001 Academic Press.