The C-elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification

The basic helix-loop-helix transcription factor NeuroD (Neurod1) has been i mplicated in neuronal fate determination, differentiation and survival. Her e we report the expression and functional analysis of end-1, a C. elegans N euroD homolog. cnd-1 expression was first detected in neuroblasts of the AB lineage in 14 cell embryos and maintained in many neuronal descendants of the AB lineage during embryogenesis, diminishing in most terminally differe ntiated neurons prior to hatching. Specifically, cnd-1 reporter genes were expressed in the precursors of the embryonic ventral cord motor neurons and their progeny. A loss-of-function mutant, cnd-1(ju29), exhibited multiple defects in the ventral cord motor neurons. First, the number of motor neuro ns was reduced, possibly caused by the premature withdrawal of the precurso rs from mitotic cycles. Second, the strict correlation between the fate of a motor neuron with respect to its lineage and position in the ventral cord was disrupted, as manifested by the variable expression pattern of motor n euron fate specific markers. Third, motor neurons also exhibited defects in terminal differentiation characteristics including axonal morphology and s ynaptic connectivity. Finally, the expression patterns of three neuronal ty pe-specific transcription factors, unc-3, unc-4 and unc-30, were altered. O ur data suggest that cnd-1 may specify the identity of ventral cord motor n eurons both by maintaining the mitotic competence of their precursors and b y modulating the expression of neuronal type-specific determination factors . cnd-1 appears to have combined the functions of several vertebrate neurog enic bHLH proteins and may represent an ancestral form of this protein fami ly.