Motor neurons are a widely studied model of vertebrate neurogenesis. They c
an be subdivided in somatic, branchial and visceral motor neurons. Recent s
tudies on the dorsoventral patterning of the rhombencephalon have implicate
d the homeobox genes Pax6 and Nkx2.2 in the early divergence of the transcr
iptional programme of hindbrain somatic and visceral motor neuronal differe
ntiation. We provide genetic evidence that the paired-like homeodomain prot
ein Phox2b is required for the formation of all branchial and visceral, but
not somatic, motor neurons in the hindbrain. In mice lacking Phox2b, both
the generic and subtype-specific programs of motoneuronal differentiation a
re disrupted at an early stage. Most motor neuron precursors die inside the
neuroepithelium while those that emigrate to the mantle layer fail to swit
ch on early postmitotic markers and to downregulate neuroepithelial markers
, Thus, the loss of function of Phox2b in hindbrain motor neurons exemplifi
es a novel control point in the generation of CNS neurons.