Distinct roles for secreted semaphorin signaling in spinal motor axon guidance.
Neuropilins, secreted semaphorin coreceptors, are expressed in discrete populations of spinal motor neurons, suggesting they provide critical guidance information for the establishment of functional motor circuitry. We show here that motor axon growth and guidance are impaired in the absence of Sema3A-Npn-1 signaling. Motor axons enter the limb precociously, showing that Sema3A controls the timing of motor axon in-growth to the limb. Lateral motor column (LMC) motor axons within spinal nerves are defasciculated as they grow toward the limb and converge in the plexus region. Medial and lateral LMC motor axons show dorso-ventral guidance defects in the forelimb. In contrast, Sema3F-Npn-2 signaling guides the axons of a medial subset of LMC neurons to the ventral limb, but plays no major role in regulating their fasciculation. Thus, Sema3A-Npn-1 and Sema3F-Npn-2 signaling control distinct steps of motor axon growth and guidance during the formation of spinal motor connections.
Huber
Andrea B
AB
Howard Hughes Medical Institute, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kania
Artur
A
Tran
Tracy S
TS
Gu
Chenghua
C
De Marco Garcia
Natalia
N
Lieberam
Ivo
I
Johnson
Dontais
D
Jessell
Thomas M
TM
Ginty
David D
DD
Kolodkin
Alex L
AL
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D001917:Brachial Plexus / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D005552:Forelimb / Q000196:embryology / Q000294:innervation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006614:Hindlimb / Q000196:embryology / Q000294:innervation; D018878:Limb Buds / Q000196:embryology / Q000294:innervation; D008160:Lumbosacral Plexus / Q000196:embryology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D039921:Neuropilins / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; D039921:Neuropilins; C488217:Sema3a protein, mouse; C491229:Sema3f protein, mouse; D040121:Semaphorin-3A; D039961:Semaphorins; D039942:Neuropilin-1