Plexin A3 and plexin A4 convey semaphorin signals during facial nerve development.
In vertebrates, class 3 semaphorins (SEMA3) control axon behaviour by binding to neuronal cell surface receptors composed of a ligand binding subunit termed neuropilin (NRP) and a signal transduction subunit of the A-type plexin family (PLXNA). We have determined the requirement for SEMA3/NRP/PLXN signalling in the development of the facial nerve, which contains axons from two motor neuron populations, branchiomotor and visceromotor neurons. Loss of either SEMA3A/NRP1 or SEMA3F/NRP2 caused defasciculation and ectopic projection of facial branchiomotor axons. In contrast, facial visceromotor axons selectively required SEMA3A/NRP1. Thus, the greater superficial petrosal nerve was defasciculated, formed ectopic projections and failed to branch in its target area when either SEMA3A or NRP1 were lost. To examine which A-type plexin conveyed SEMA3/neuropilin signals during facial nerve development, we combined an expression analysis with loss of function studies. Even though all four A-type plexins were expressed in embryonic motor neurons, PLXNA1 and PLXNA2 were not essential for facial nerve development. In contrast, loss of PLXNA4 phenocopied the defects of SEMA3A and NRP1 mutants, and loss of PLXNA3 phenocopied the defects of SEMA3F and NRP2 mutants. The combined loss of PLXNA3 and PLXNA4 impaired facial branchiomotor axon guidance more severely than loss of either plexin alone, suggesting that SEMA3A and SEMA3F signals, even though both essential, are partially redundant.
Schwarz
Quenten
Q
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Waimey
Kathryn E
KE
Golding
Matthew
M
Takamatsu
Hyota
H
Kumanogoh
Atsushi
A
Fujisawa
Hajime
H
Cheng
Hwai-Jong
HJ
Ruhrberg
Christiana
C
D000818:Animals; D001369:Axons / Q000502:physiology; D005154:Facial Nerve / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D039942:Neuropilin-1 / Q000235:genetics / Q000502:physiology; D039943:Neuropilin-2 / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C492112:Plxna3 protein, mouse; C492110:Plxna4 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins; D039942:Neuropilin-1