Angiogenesis within the developing mouse neural tube is dependent on sonic hedgehog signaling: possible roles of motor neurons.
Embryonic morphogenesis of vascular and nervous systems is tightly coordinated, and recent studies revealed that some neurogenetic factors such as Sonic hedgehog (Shh) also exhibit angiogenetic potential. Vascularization within the developing mouse neural tube depends on vessel sprouting from the surrounding vascular plexus. Previous studies implicated possible roles of VEGF/Flk-1 and Angiopoietin-1(Ang-1)/Tie-2 signaling as candidate molecules functioning in this process. Examining gene expressions of these factors at embryonic day (E) 9.5 and 10.5, we unexpectedly found that both VEGF and Ang-1 were expressed in the motor neurons in the ventral neural tube. The motor neurons were indeed located in the close vicinity of the infiltrating vessels, suggesting involvement of motor neurons in the sprouting. To substantiate this possibility, we inhibited induction of the motor neurons in the cultured mouse embryos by cyclopamine, a Shh signaling blocker. The vessel sprouting was dramatically impaired by inhibition of Shh signaling, together with nearly complete loss of the motor neurons. Expression of Ang-1, but not VEGF, within the neural tube was remarkably reduced in the cyclopamine treated embryos. These results suggest that the neural tube angiogenesis is dependent on Shh signaling, and mediated, at least in part, by the Ang-1 positive motor neurons.
Nagase
Takashi
T
Department of Plastic and Reconstructive Surgery, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. tnagase@fb3.so-net.ne.jp
Nagase
Miki
M
Yoshimura
Kotaro
K
Fujita
Toshiro
T
Koshima
Isao
I
D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D009046:Motor Neurons / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009672:Notochord / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction; D013723:Teratogens / Q000494:pharmacology; D046509:Tissue Culture Techniques; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000494:pharmacology
D042683:Angiopoietin-1; D053823:Hedgehog Proteins; D013723:Teratogens; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D014704:Veratrum Alkaloids; C000541:cyclopamine