The differentiation of a proliferating neural progenitor into a postmitotic neuronal cell is a critical transition during mammalian neural development. During this time period, extensive cell lineage commitments are formed based on signals from dorsoventral and anteroposterior signaling centers

The differentiation of a proliferating neural progenitor into a postmitotic neuronal cell is a critical transition during mammalian neural development. During this time period, extensive cell lineage commitments are formed based on signals from dorsoventral and anteroposterior signaling centers (Altmann and Brivanlou, 2001; Briscoe et al., 2000; Chiang et al., 1996; Lee et al., 2000). These signals are integrated with cues controlling the timing of differentiation, such as those modulated by the effects of lateral inhibition (Cai et al., 2000; Gaiano et al., 2000; Morrison et al., 2000). The neural bHLH family of transcription factors, which is expressed in specific populations of neural precursors, figure prominently in this process. The regulation of these transcription factors, including Mash1 (Ascl1 – Mouse Genome Informatics), Math1 (Atoh1 – Mouse Genome Informatics) and Ngn1 (Neurog1 – Mouse Genome Informatics) may serve to translate dorsoventral positional information into specific neural cell-type identity (Fode et al., 2000; Gowan et al., 2001; Lee et al., 2000; Lee et al., 1998). Accordingly, the expression of bHLH genes in a restricted pattern appears to be required for the generation of a diverse population of adult neurons. Loss-of-function mutations in these factors result in the loss of specific subsets of neurons and neonatal lethality (Ben-Arie et al., 1997; Bermingham et al., 1999; Bermingham et al., 2001; Fode et al., 1998; Guillemot et al., 1993; Ma et al., 1998). Overexpression of these neural bHLH factors appears to induce neuronal differentiation (Cai et al., 2000; Farah et al., 2000; Kim et al., 1997; Lee et al., 1995; Ma et al., 1996; Sun et al., 2001). In addition, substantial defects in neural development arise when the expression of Math1 is deregulated spatially, temporally or quantitatively (Helms et al., 2001; Isaka et al., 1999). Thus, the proper initiation, maintenance and termination of neural bHLH transcription factor expression are essential for normal neural development. The bHLH factor Math1 is expressed transiently in proliferating neural precursors in multiple domains of the developing murine nervous system, including the dorsal hindbrain and neural tube, hair cells of the vestibular and auditory systems, mechanoreceptor (Merkel) cells of the hairy skin, and the cells of the external granule layer of the developing cerebellum (Akazawa et al., 1995; Ben-Arie et al., 2000; Ben-Arie et al., 1996; Helms and Johnson, 1998). Analysis of the Math1 gene has identified two discrete ~500 bp sequences 3′ of the Math1-coding sequence that exhibit significant homology to sequences flanking the human ortholog HATH1 (ATOH1 – Human Gene Nomenclature 1949 Development 130, 1949-1959 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00419