NEUROM, A NEURAL HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, DEFINES A NEWTRANSITION STAGE IN NEUROGENESIS

Genes encoding transcription factors of the helix-loop-helix family ar e essential for the development of the nervous system in Drosophila an d vertebrates. Screens of an embryonic chick neural cDNA library have yielded NeuroM, a novel neural-specific helix-loop-helix transcription factor related to the Drosophila proneural gene atonal. The NeuroM pr otein most closely resembles the vertebrate NeuroD and Nex1/MATH2 fact ors, and is capable of transactivating an E-box promoter in vivo. In s itu hybridization studies have been conducted, in conjunction with pul se-labeling of S-phase nuclei, to compare NeuroM to NeuroD expression in the developing nervous system. In spinal cord and optic tectum, Neu roM expression precedes that of NeuroD. It is transient and restricted to cells lining the ventricular zone that have ceased proliferating b ut have not yet begun to migrate into the outer layers. In retina, Neu roM is also transiently expressed in cells as they withdraw from the m itotic cycle, but persists in horizontal and bipolar neurons until ful l differentiation, assuming an expression pattern exactly complementar y to NeuroD. In the peripheral nervous system, NeuroM expression close ly follows cell proliferation, suggesting that it intervenes at a simi lar developmental juncture in all parts of the nervous system. We prop ose that availability of the NeuroM helix-loop-helix factor defines a new stage in neurogenesis, at the transition between undifferentiated, premigratory and differentiating, migratory neural precursors.