膜生物学・医学学術講演会

⼤学院特別講義/膜⽣物学・医学学術講演会
場所/臨床研究棟5階 B講義室
⽇時/平成28年3⽉30⽇(⽔) 17時〜18時
ｺｰﾃﾞｨﾈｰﾀｰ：細胞⽣理学分野教授/南康博主催：膜⽣物学・医学教育研究ｾﾝﾀｰ
連絡先：研究⽀援課研究企画係 TEL：5195/MAIL：[email protected]
先端医学トピックスの講義としても開講します
発⽣と疾患における
Wnt/PCPシグナル
Wnt/PCP signaling in development and disease
Prof. Yingzi Yang
Dept. of DevelopmentalBiology
Harvard University School of Dental Medicine
Harvard Stem Cell Institute
Yang教授は、発⽣の形態形成において重要な役割を担うWnt/PCPシグナル研究の第⼀⼈者であり、本年3
⽉末に開催されるRIKENシンポジウム「Size in Development: Growth, Shape and Allometry」に招聘
演者として来神されます。この度、この機会に本研究科においてWnt/PCPシグナル研究の新たな展開につ
いてご講演頂くこととなりました。奮ってご参加ください。
【参考⽂献】Annu. Rev. Cell Dev. Biol. 31: 623-646, 2015; Nature Med. 19: 1505-1512,
2013;Curr. Opin. Genet. Dev. 23: 438-444, 2013; Dev. Cell 20:163-176, 2011; Nature 466:
378-382, 2010 他多数。
【ABSTRACT】Directed cellular polarization as a key feature of organismal development is required for
tissue and organ function and homeostasis. Planar Cell Polarity (PCP) is emerging as a fundamental
mechanism regulating various morphogenetic processes including cartilage elongation in the limb, anteriorposterior (A-P) body axis elongation, neural tube closure, body hair orientation, orientation of inner ear
sensory hair cells, left-right asymmetry and axon guidance in vertebrates. Mutations in PCP signaling
components have been identified in human diseases such as brachydactyly type B1, Robinow syndrome,
scoliosis, spinal bifida and epilepsy. Despite the fundamentally important roles of PCP, the mechanisms of
PCP establishment by global instructive cues such as Wnts remain poorly understood and represent an
exciting frontier in developmental and cell biology. The Wnt/Planar Cell Polarity (PCP) pathway is
evolutionarily conserved and provides essential directional information during morphogenesis to orient
cytoskeleton, cell division, cell migration, differential adhesion across cells, and to position cell extensions,
such as cilia and axons. However, unlike the extensively studied Wnt/b-catenin pathway, Wnt signal
transduction in the PCP pathway remains poorly understood. The PCP pathway is controlled by core PCP
proteins including Van Gogh (Vang), Frizzled (Fzd) and Dishevelled (Dvl), which were originally identified in
Drosophila. Wnt/PCP signaling in vertebrates is more complex and functionally diverse and vertebratespecific features of PCP require rigorous genetic and biochemical studies of their own. The core PCP
proteins are initially randomly distributed in the cell and gradually accumulate on one side of the cells
instructed by global cues during PCP establishment. We have found that Wnt5a is a global cue required for
establishing PCP in vertebrate long bone cartilage by inducing a novel receptor complex that contains Vang
like 2 (Vangl2) and Ror2, a vertebrate specific PCP component. As a result, Vangl2 is phosphorylated in a
Wnt5a dose-dependent manner and Vangl2 phosphorylation regulates its function. Our identification of
Wnt induced PCP signalosome and Vangl2 phosphorylation as both an important readout and transducer of
Wnt/PCP signaling opens a new door to find missing links in the Wnt/PCP signaling cascade. More recently,
we have found that Wnt5a interacts with Fgf8 signaling in coordinating proximal-distal limb elongation.

Download Report