Transcriptional Cascades to Regulate Neuronal Differentiation by Mammalian Barh1 (MBH1)

Abstract

The vertebrate nervous system comprises an enormous number of cell types, of which differentiation is controlled by a combination of regulators. Members of basic-helix-loop-helix (bHLH) transcription factors play important roles in vertebrate neurogenesis. A mammalian homologue of achaete-scute, Mash1, is required for the differentiation of autonomic, olfactory sensory, and some ventral forebrain neurons, neuro genius (ngns), which encode Atonal-related bHLH factors, control the differentiation of some central nervous system (CNS) neurons and sensory neurons in the cranial and dorsal root ganglia. Mash1 and ngns are expressed in distinct subsets or areas of cells giving rise to neurons. The distinct expression patterns of these genes suggest that they play important roles in generating the diversity of neuronal cell types. However, molecular mechanisms of neuronal differentiation at early stages, such as upstream regulators of the bHLH genes, are less well characterized. In order to find genes which function at the early stages, we have applied the differential PCR method to developing CNS tissues and cloned several genes. One of the genes was a Bar-class homeobox (Barh) gene and named MBH1. MBH1 is most closely related to the Drosophila BarH1 and BarH2 genes.