Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b.
Motor neurons are a widely studied model of vertebrate neurogenesis. They can be subdivided in somatic, branchial and visceral motor neurons. Recent studies on the dorsoventral patterning of the rhombencephalon have implicated the homeobox genes Pax6 and Nkx2.2 in the early divergence of the transcriptional programme of hindbrain somatic and visceral motor neuronal differentiation. We provide genetic evidence that the paired-like homeodomain protein 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 are disrupted at an early stage. Most motor neuron precursors die inside the neuroepithelium while those that emigrate to the mantle layer fail to switch on early postmitotic markers and to downregulate neuroepithelial markers. Thus, the loss of function of Phox2b in hindbrain motor neurons exemplifies a novel control point in the generation of CNS neurons.
Pattyn
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Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM/Univ Méditerranée/AP de Marseille, Luminy Case 907, France.
Hirsch
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Goridis
C
C
Brunet
J F
JF
D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006579:Heterozygote; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D017403:In Situ Hybridization; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008959:Models, Neurological; D009046:Motor Neurons / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D017931:DNA Primers; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; C000715627:Nkx2-2 protein, mouse; D014157:Transcription Factors