Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates.
There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral neuronal fate in the vertebrate central nervous system through Nkx-class homeodomain proteins. We have examined the patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons. At many axial levels there is a complete block in the generation of V2 interneurons and motor neurons and a compensatory ventral expansion in the domain of generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in regional patterning and neuronal fate determination.
Sander
M
M
Hormone Research Institute, Department of Medicine, University of California-San Francisco, San Franscisco, California 94143, USA.
Paydar
S
S
Ericson
J
J
Briscoe
J
J
Berber
E
E
German
M
M
Jessell
T M
TM
Rubenstein
J L
JL
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019070:Cell Lineage; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D018390:Gene Targeting; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C516210:ISL2 protein, human; C091135:Isl-2 protein, vertebrate; C558561:Isl2 protein, mouse; C094898:Lhx3 protein; C491328:Nkx6-1 protein, mouse; C497319:Pax2 protein, mouse; C509239:SHH protein, human; C491094:SIM1 protein, human; C101750:Sim1 protein, mouse; C490289:VSX2 protein, human; C088975:Vsx2 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1