Active suppression of interneuron programs within developing motor neuronsrevealed by analysis of homeodomain factor HB9

Sonic hedgehog (Shh) specifies the identity of both motor neurons (MNs) and interneurons with morphogen-like activity. Here, we present evidence that the homeodomain factor HB9 is critical for distinguishing MN and interneuro n identity in the mouse. Presumptive MN progenitors and postmitotic MNs exp ress HB9, whereas interneurons never express this factor. This pattern rese mbles a composite of the avian homologs MNR2 and HB9. In mice lacking Hb9, the genetic profile of MNs is significantly altered, particularly by upregu lation of Chx10, a gene normally restricted to a class of ventral interneur ons. This aberrant gene expression is accompanied by topological disorganiz ation of motor columns, loss of the phrenic and abducens nerves, and interc ostal nerve pathfinding defects. Thus, MNs actively suppress interneuron ge netic programs to establish their identity.