title: The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish.
abstract: Blood vessels and neurons grow often side by side. However, the molecular and cellular mechanisms underlying their parallel development remain unclear. Here, we report that a subpopulation of secondary motoneurons extends axons ventrally outside of the neural tubes and rostrocaudally as a fascicle beneath the dorsal aorta (DA) in zebrafish. We tried to clarify the mechanism by which these motoneuron axons grow beneath the DA and found that Vegfc in the DA and Vegfr3 in the motoneurons were essential for the axon growth. Forced expression of either Vegfc in arteries or Vegfr3 in motoneurons resulted in enhanced axon growth of motoneurons over the DA. Both vegfr3 morphants and vegfc morphants lost the alignment of motoneuron axons with DA. In addition, forced expression of two mutant forms of Vegfr3 in motoneurons, potentially trapping endogenous Vegfc, resulted in failure of growth of motoneuron axons beneath the DA. Finally, a vegfr3 mutant fish lacked the motoneuron axons beneath the DA. Collectively, Vegfc from the preformed DA guides the axon growth of secondary motoneurons.
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Hyouk-Bum
authors.initials: HB
authors.lastname: Kwon
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Asakawa
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.forename: Takeru
authors.initials: T
authors.lastname: Kashiwada
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hibi
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D042582:Vascular Endothelial Growth Factor C; D029961:Zebrafish Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Guidance; Motoneuron; Vegfc; Vegfr3; Wiring
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