LINEAGE-SPECIFIC REGULATION OF THE NEURAL DIFFERENTIATION GENE MASH1

Mash1 is a transcription factor required during embryogenesis for the development of multiple neural lineages. It is expressed in restricted domains at specific stages in the developing central and peripheral n ervous systems and in the developing olfactory epithelium. We have inv estigated the regulation of Mash1 expression during embryogenesis usin g transgenic mice containing Mash1/lacZ reporter constructs. Cis-actin g regulatory elements controlling Mash1 expression in the central nerv ous system are located within an 8-kb sequence upstream of the Mash1 c oding region. This 8-kb sequence does not contain elements directing e xpression to the peripheral nervous system, olfactory epithelium, or r etina. Sequences outside this 8 kb but within 36 kb of the Mash1 locus contain elements responsible for expression in the autonomic division of the peripheral nervous system. However, transgene expression in em bryos containing the 36-kb sequence was never detected in the olfactor y epithelium and retina. Thus, regulatory elements driving expression in these lineages may be at even greater distances from the Mash1 codi ng region. These data provide evidence for complex regulation of Mash1 expression in which multiple lineage-specific cis-acting regulatory r egions span greater than 36 kb of the Mash1 locus. Further characteriz ation of these regions will facilitate the study of factors that regul ate the temporal and spatial expression of Mash1 during development. I n addition, the regulatory sequences identified here can direct expres sion of heterologous genes to developing neural lineages that normally express Mash1, thus providing an important tool for examining the fun ction of candidate regulatory genes in mammalian nervous system develo pment. (C) 1996 Academic Press, Inc.