Differential requirement for Plexin-A3 and -A4 in mediating responses of sensory and sympathetic neurons to distinct class 3 Semaphorins.
The class 3 Semaphorins Sema3A and Sema3F are potent axonal repellents that cause repulsion by binding Neuropilin-1 and Neuropilin-2, respectively. Plexins are implicated as signaling coreceptors for the Neuropilins, but the identity of the Plexins that transduce Sema3A and Sema3F responses in vivo is uncertain. Here, we show that Plexin-A3 and -A4 are key determinants of these responses, through analysis of a Plexin-A3/Plexin-A4 double mutant mouse. Sensory and sympathetic neurons from the double mutant are insensitive to Sema3A and Sema3F in vitro, and defects in axonal projections in vivo correspond to those seen in Neuropilin-1 and -2 mutants. Interestingly, we found a differential requirement for these two Plexins: signaling via Neuropilin-1 is mediated principally by Plexin-A4, whereas signaling via Neuropilin-2 is mediated principally by Plexin-A3. Thus, Plexin-A3 and -A4 contribute to the specificity of axonal responses to class 3 Semaphorins.
Yaron
Avraham
A
Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Huang
Pei-Hsin
PH
Cheng
Hwai-Jong
HJ
Tessier-Lavigne
Marc
M
D000483:Alleles; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D015139:Blotting, Southern / Q000379:methods; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018920:Coculture Techniques / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D040121:Semaphorin-3A / Q000378:metabolism*; D014162:Transfection
D000596:Amino Acids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C492112:Plxna3 protein, mouse; C492110:Plxna4 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C488217:Sema3a protein, mouse; C491229:Sema3f protein, mouse; D040121:Semaphorin-3A; C098463:dolaisoleucine