Different levels of repressor activity assign redundant and specific rolesto Nkx6 genes in motor neuron and interneuron specification

Specification of neuronal fate in the vertebrate central nervous system dep ends on the profile of transcription factor expression by neural progenitor cells, but the precise roles of such factors in neurogenesis remain poorly characterized. Two closely related transcriptional repressors, Nkx6.2 and Nkx6.1, are expressed by progenitors in overlapping domains of the ventral spinal cord. We provide genetic evidence that differences in the level of r epressor activity of these homeodomain proteins underlies the diversificati on of interneuron subtypes, and provides a fail-safe mechanism during motor neuron generation. A reduction in Nkx6 activity further permits VO neurons to be generated from progenitors that lack homeodomain proteins normally r equired for their generation, providing direct evidence for a model in whic h progenitor homeodomain proteins direct specific cell fates by actively su ppressing the expression of transcription factors that direct alternative f ates.