Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity.
The fidelity with which spinal motor neurons innervate their limb target muscles helps to coordinate motor behavior, but the mechanisms that determine precise patterns of nerve-muscle connectivity remain obscure. We show that Nkx6 proteins, a set of Hox-regulated homeodomain transcription factors, are expressed by motor pools soon after motor neurons leave the cell cycle, before the formation of muscle nerve side branches in the limb. Using mouse genetics, we show that the status of Nkx6.1 expression in certain motor neuron pools regulates muscle nerve formation, and the pattern of innervation of individual muscles. Our findings provide genetic evidence that neurons within motor pools possess an early transcriptional identity that controls target muscle specificity.
De Marco Garcia
Natalia V
NV
Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA.
Jessell
Thomas M
TM
D000367:Age Factors; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002642:Chick Embryo; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006614:Hindlimb / Q000196:embryology / Q000294:innervation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009046:Motor Neurons / Q000502:physiology*; D009121:Muscle Denervation / Q000379:methods; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C491328:Nkx6-1 protein, mouse; D049452:Green Fluorescent Proteins; D006735:Horseradish Peroxidase