Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways

The diverse neuronal subtypes in the adult central nervous system arise from progenitor cells specified by the combined actions of anteroposterior (AP) and dorsoventral (DV) signaling molecules in the neural tube. Analyses of the expression and targeted disruption of the homeobox gene Hoxb1 demonstrate that it is essential for patterning progenitor cells along the entire DV axis of rhombomere 4 (r4). Hoxb1 accomplishes this function by acting very early during hindbrain neurogenesis to specify effectors of the sonic hedgehog and Mash1 signaling pathways. In the absence of Hoxb1 function, multiple neurons normally specified within r4 are instead programmed for early cell death. The findings reported here provide evidence for a genetic cascade in which an AP-specified transcription factor, Hoxb1, controls the commitment and specification of neurons derived from both alar and basal plates of r4.