title: PlexinA4 is necessary as a downstream target of Islet2 to mediate Slit signaling for promotion of sensory axon branching.
abstract: Slit is a secreted protein known to repulse the growth cones of commissural neurons. By contrast, Slit also promotes elongation and branching of axons of sensory neurons. The reason why different neurons respond to Slit in different ways is largely unknown. Islet2 is a LIM/homeodomain-type transcription factor that specifically regulates elongation and branching of the peripheral axons of the primary sensory neurons in zebrafish embryos. We found that PlexinA4, a transmembrane protein known to be a co-receptor for class III semaphorins, acts downstream of Islet2 to promote branching of the peripheral axons of the primary sensory neurons. Intriguingly, repression of PlexinA4 function by injection of the antisense morpholino oligonucleotide specific to PlexinA4 or by overexpression of the dominant-negative variant of PlexinA4 counteracted the effects of overexpression of Slit2 to induce branching of the peripheral axons of the primary sensory neurons in zebrafish embryos, suggesting involvement of PlexinA4 in the Slit signaling cascades for promotion of axonal branching of the sensory neurons. Colocalized expression of Robo, a receptor for Slit2, and PlexinA4 is observed not only in the primary sensory neurons of zebrafish embryos but also in the dendrites of the pyramidal neurons of the cortex of the mammals, and may be important for promoting the branching of either axons or dendrites in response to Slit, as opposed to the growth cone collapse.
authors.affiliation: Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyashita
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Yeo
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirate
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Segawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Wada
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Little
authors.forename: Toshiya
authors.initials: T
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology*; D029961:Zebrafish Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C091135:Isl-2 protein, vertebrate; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C490404:isl2a protein, zebrafish; C491030:plxna4 protein, zebrafish; D000098552:Slit Homolog 2 Protein