A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons.
Motor neurons, alone among neurons in the vertebrate CNS, extend axons out of the neural tube to innervate peripheral targets. Two classes of motor neurons, termed vMNs and dMNs, extend axons out of the neural tube via ventral and dorsal exit points, respectively, in accord with their homeodomain transcription factor repertoire. Downstream of these transcriptional codes, the cell surface receptors that shape initial motor axon trajectories have not been identified. We show here that the chemokine receptor Cxcr4 is expressed on the axons of vMNs as they follow their ventral trajectory, whereas its ligand, Cxcl12, is expressed by mesenchymal cells surrounding the ventral neural tube. Genetic studies reveal that Cxcl12-Cxcr4 signaling directs the ventral trajectory of spinal vMNs. In its absence, these neurons adopt a dMN-like trajectory, despite preservation of their vMN transcriptional identity. Thus, the status of Cxcr4 signaling helps to determine the initial axonal trajectory of mammalian motor neurons.
Lieberam
Ivo
I
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, New York, New York 10032, USA.
Agalliu
Dritan
D
Nagasawa
Takashi
T
Ericson
Johan
J
Jessell
Thomas M
TM
D000818:Animals; D001369:Axons / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D018925:Chemokines / Q000502:physiology*; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020439:Growth Cones / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012249:Rhombencephalon / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology
D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger