title: Angiogenesis in the developing spinal cord: blood vessel exclusion from neural progenitor region is mediated by VEGF and its antagonists.
abstract: Blood vessels in the central nervous system supply a considerable amount of oxygen via intricate vascular networks. We studied how the initial vasculature of the spinal cord is formed in avian (chicken and quail) embryos. Vascular formation in the spinal cord starts by the ingression of intra-neural vascular plexus (INVP) from the peri-neural vascular plexus (PNVP) that envelops the neural tube. At the ventral region of the PNVP, the INVP grows dorsally in the neural tube, and we observed that these vessels followed the defined path at the interface between the medially positioned and undifferentiated neural progenitor zone and the laterally positioned differentiated zone. When the interface between these two zones was experimentally displaced, INVP faithfully followed a newly formed interface, suggesting that the growth path of the INVP is determined by surrounding neural cells. The progenitor zone expressed mRNA of vascular endothelial growth factor-A whereas its receptor VEGFR2 and FLT-1 (VEGFR1), a decoy for VEGF, were expressed in INVP. By manipulating the neural tube with either VEGF or the soluble form of FLT-1, we found that INVP grew in a VEGF-dependent manner, where VEGF signals appear to be fine-tuned by counteractions with anti-angiogenic activities including FLT-1 and possibly semaphorins. These results suggest that the stereotypic patterning of early INVP is achieved by interactions between these vessels and their surrounding neural cells, where VEGF and its antagonists play important roles.
authors.affiliation: Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan; Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Takase
authors.affiliation: Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saito
authors.affiliation: Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tadokoro
authors.affiliation: Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D018919:Neovascularization, Physiologic / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism*; D054259:Neural Tube / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology*; D011784:Quail; D013116:Spinal Cord / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2