A homeodomain protein code specifies progenitor cell identity and neuronalfate in the ventral neural tube

Distinct classes of neurons are generated at defined positions in the ventr al neural tube in response to a gradient of Sonic Hedgehog (Shh) activity. A set of homeodomain transcription factors expressed by neural progenitors act as intermediaries in Shh-dependent neural patterning. These homeodomain factors fall into two classes: class I proteins are repressed by Shh and c lass II proteins require Shh signaling for their expression. The profile of class I and class II protein expression defines five progenitor domains, e ach of which generates a distinct class of postmitotic neurons. Cross-repre ssive interactions between class I and class II proteins appear to refine a nd maintain these progenitor domains. The combinatorial expression of three of these proteins-Nkx6.1, Nkx2.2, and Irx3-specifies the identity of three classes of neurons generated in the ventral third of the neural tube.