Semaphorin Signalling in Neuronal and Vascular Development in the Tooth
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Background: The tooth is a well-established model in which to study molecular signaling that regulates organ morphogenesis. Previously, organ-specific innervation of the tooth and its molecular regulation has, to some extent, been investigated. The findings show that semaphorin (Sema) signaling is required for innervation of the tooth and that semaphorin signalling is under local control of signaling molecules produced by the tooth. On the other hand, development of dental vasculature, and its regulation and relationship to dental innervation, is currently still obscure. Objectives: To investigate in detail development of tooth vascularization during embryogenesis and in the postnatal crown and early root development. Moreover, to compare the early development of tooth vasculature and innervation. To examine, in addition, expression of VEGF mRNAs during tooth organogenesis, as well as in vivo functions of SEMA3A and SEMA6A signaling in the development of tooth vasculature, innervation and morphogenesis. Materials and methods: RT-PCR on embryonic tooth germs and in situ hybridization on histological sections were applied in order to analyse and localize mRNAs. Immunohistochemistry was used to localize proteins in tissue sections. Sema3A and -6A-deficient mouse mandibular first molar tooth germs and wild-type teeth were used as model organ systems. Results: Growth and branching of dental blood vessels and expression VEGF mRNAs during early odontogenesis are regulated in the course of development. Sema6A-deficient mice show defects in timing of tooth innervation, but SEM3A and -6A are dispensable for the development of tooth blood vessels. Conclusions: Both the maturation of tooth nerve supply and blood vessels are developmentally but differentially regulated, and VEGF is suggested to serve key functions in the development of tooth vasculature. SEM3A and -6A signaling regulates tooth innervation but does not appear to play any essential role in tooth histomorphogenesis or development of its supporting tissues such as blood vessels in vivo. Consequences: Further experimental and molecular investigations are warranted with regard to gaining a better understanding of regulation of dental vascular development, and maturation, as well as the putative functions of VEGF signaling on growth and patterning of blood vessels and neurites in the developing tooth.
Består avPaper I: Omnia Shadad*, Rajib Chaulagain*, Keijo Luukko and Paivi Kettunen. Establishment of tooth blood supply and innervation is developmentally regulated and takes place through differential patterning process. Full text not available in BORA.
Paper II: Omnia Shadad, Paivi Kettunen, Masahiko Taniguchi and Keijo Luukko. Dental vasculature develops independently of SEMA3A signaling and sensory innervation. Full text not available in BORA.
Paper III: Omnia Shadad, Kevin Mitchell, Keijo Luukko and Paivi Kettunen. SEMA6A regulates sensory innervation, but is dispensable for vascular development and tooth morphogenesis. Full text not available in BORA.