Neuron 2005 Feb
Yaron A, Huang PH, Cheng HJ, Tessier-Lavigne M
Abstract
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 doub
...[more]le 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.
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Mesh Headings:
Alleles, Amino Acids, Animals, Axons, Blotting, Northern, Blotting, Southern, Brain, Cells, Cultured, Cercopithecus aethiops, Coculture Techniques, Embryo, Mammalian, Gene Expression Regulation, Developmental, Genotype, Immunohistochemistry, Membrane Proteins, Mice, Mice, Knockout, Models, Biological, Nerve Tissue Proteins, Neurofilament Proteins, Neurons, Afferent, Peripheral Nervous System, RNA, Messenger, Receptors, Cell Surface, Reverse Transcriptase Polymerase Chain Reaction, Semaphorin-3A, Transfection