Proneural gene Mash1 (Ascl1) is expressed in multiple lineages and regulates their differentiation and specification.

Ascl1 (Mash1), a bHLH transcription factor, is widely expressed by neuronal progenitors. The gene plays a key role in the differentiation of the autonomic nervous system, i.e., sympathetic, parasympathetic, and enteric ganglia; all of which are derived from neural crest cells. In Ascl1-null mutants, defective development of these ganglia is induced. The differentiation of neuroendocrine cells, including the carotid body, ultimobranchial body and thyroid C cells, the neuroepithelial body in the lung, and the adrenal medulla, is also controlled by Ascl1. Although the carotid body glomus cells and adrenal medulla are derived from neural crest, the ultimobranchial body is from pharyngeal endoderm and the neuroepithelial body is from endodermal epithelium. A targeted mutation of Ascl1 results in complete loss or failure in differentiation of these neuroendocrine cells. Furthermore, the development of olfactory epithelium and bulbus is regulated by Ascl1. In the central nervous system, Ascl1 is expressed in the arcuate and ventromedial nuclei, telencephalon, and dopaminergic neurons such as locus coeruleus and nucleus tractus solitarius. The elimination or atrophy of these regions are induced in Ascl1-null mutants. All cells and tissues affected by the deficiency of Ascl1 express catecholamines and/or serotonin. The Phox2b or/and Hes1 genes are required for regulation of Ascl1 expression. Phox2b stimulates the expression of Ascl1, whereas Hes1 represses gene expression.