Active suppression of interneuron programs within developing motor neurons revealed 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 interneuron identity in the mouse. Presumptive MN progenitors and postmitotic MNs express HB9, whereas interneurons never express this factor. This pattern resembles a composite of the avian homologs MNR2 and HB9. In mice lacking Hb9, the genetic profile of MNs is significantly altered, particularly by upregulation of Chx10, a gene normally restricted to a class of ventral interneurons. This aberrant gene expression is accompanied by topological disorganization of motor columns, loss of the phrenic and abducens nerves, and intercostal nerve pathfinding defects. Thus, MNs actively suppress interneuron genetic programs to establish their identity.
Thaler
J
J
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Harrison
K
K
Sharma
K
K
Lettieri
K
K
Kehrl
J
J
Pfaff
S L
SL
D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D005801:Genes, Homeobox / Q000235:genetics*; D053823:Hedgehog Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000502:physiology
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C490006:MNX1 protein, Xenopus; D012097:Repressor Proteins; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; D029867:Xenopus Proteins; C084059:Hb9 protein, mouse