Motor neurons with axial muscle projections specified by Wnt4/5 signaling.
Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Wnts appear to establish a ventral(high) to dorsal(low) signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.
Agalliu
Dritan
D
Howard Hughes Medical Institute, Kavli Institute for Brain Science, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
Takada
Shinji
S
Agalliu
Ilir
I
McMahon
Andrew P
AP
Jessell
Thomas M
TM
D000704:Analysis of Variance; D000818:Animals; D002642:Chick Embryo; D005786:Gene Expression Regulation / Q000235:genetics; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006735:Horseradish Peroxidase / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009434:Neural Pathways / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D014157:Transcription Factors / Q000172:deficiency; D051153:Wnt Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein; D029961:Zebrafish Proteins
D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C438615:Wnt5a protein, mouse; D029961:Zebrafish Proteins; D006735:Horseradish Peroxidase