| Co-Investigator(Kenkyū-buntansha) |
HIGASHIYAMA Shigeki Osaka University Faculty of Medicine, Research Assistant, 医学部, 助手 (60202272)
MATSUURA Nariaki Osaka University Faculty of Medicine, Professor, 医学部, 教授 (70190402)
SHIGENAGA Yoshio Osaka University Dental School, Professor, 歯学部, 教授 (90028770)
ALLEN Nichol バブラハン研究所, 発生神経生物学研究部, 部長
SWANSON Larry.W. University of Southern California Biological Sciences, Professor, 生物科学部, 教授
ALLEN Nichoolas D. Babraham Institute, Laboratory of Developmental Neurology, Head
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| Research Abstract |
Axon pathfinding during neural development depends on both attractive and repulsive guidance signals.The collapsins/semaphorins are a large family of structurally distinct secreted and transmembrane proteins characterized by the presence of a conserved semaphorin domain (sema domain) of about 500 amino acids at their amino acid termini. Chick collapsin-1 (coll-1) and its mammalian homolog semaphorin D (semD) functions in vitro as a collapsing factor for gorwth cones of sensory and sympathetic neurons, and also acts as a selective chemorepellent for subpopulations of spinal and cranial, sensory and motor axons. However no or little is known on the other semaphorins. In this research, we have identified two transmembrane semaphorins, M-semaF and M-semaG,and one secreted semaphorins, M-semak. Their expression, protein distribution, and functions were analyzed in this reserach project. The mRNAs for M-semaF and M-semaG were in the neuronal tissues and and non-neuronal tissues. M-semaF expression was prominent in the immature brain and spinal cord, while M-semaG expression was found in both embryos and postnatal animals. The latter one was strongly expressed in the immune tissues such as the thymus as well as in the neuronal tissues. These results suggest that M-semaG play an important role in the immune system as well as in the nervous system. We also produced antibodies to these semaphorins, and studied the localization of the proteins in the tissues. The proteins were principally found in axons and at low levels in the neuronal cell bodies. We also confirmed the strong expression for M-SemaG on the surface of T1ymphocytes, suggesting it is involved the the interaction of T and B cells. We developed the biological assays, such as the adhesion, growth cone collapse, and coculture assays. We will furher study using those and additional assays what functions these molecules involved in and what molecules are the counter receptors for these molecules.
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