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下記の要領で、10月26日(火)午後3時より ユタ大学 西條 幸男 先生の「東京大学 農学生命科学,獣医応動公開セミナー」を農学部 7号館 A棟 で開催いたします。



演 者: 西條 幸男 准教授 
(所属:Department of Neurobiology and Anatomy&s_comma; University of Utah)

日 時: 2010年10月26日(火)15:00 - 16:00

場 所: 東京大学 農学部7号館 A棟 1階 104/105号教室
(文京区弥生1-1-1&s_comma; 千代田線 根津駅、南北線 東大駅前下車)

演 題:The Role of Endoderm in Left Right Asymmetry

要旨:Establishment of left right (LR) asymmetry is required for correct positioning and function of internal organs such as the heart&s_comma; vasculature&s_comma; lungs&s_comma; and gastrointestinal tract. Defects in human left right (LR) axis formation cause life threatening birth defects of these organ systems that are costly to the healthcare system. My long-term goal is to understand the mechanisms of LR asymmetry establishment during early embryogenesis. Our previous work has revealed 3 important steps in this process. First&s_comma; the initial symmetry break occurs in the node by the directional flow of the extra-embryonic fluid&s_comma; called ‘nodal flow’&s_comma; generated by the node cilia. Second&s_comma; the LR signal in the node is transferred from the node to the left lateral plate mesoderm (LPM)&s_comma; which is a precursor of asymmetric organs. Third&s_comma; the left side determinant Nodal&s_comma; which is regulated by positive and negative (Lefty) feedback loops&s_comma; expands to cover the entire left LPM necessary for left side specific characteristics. However&s_comma; there are still gaps in our understanding of the entire process&s_comma; such as the mechanisms by which the node structure and rotating node cilia develop&s_comma; and how LR polarity in the node is transferred to the left LPM. Here I will investigate whether or not definitive endoderm regulates both of these processes. We focused on roles of the endoderm cells in establishing LR asymmetry for the following reasons: (1) The endoderm precursors closely interact with the node precursors in the primitive streak; (2) Later in development&s_comma; the endoderm cells localize adjacent to the node and cover the LPM. (3) Increased intracellular Ca2+ levels are observed only in the left endoderm cells adjacent to the node just after Nodal flow is established&s_comma;making this the earliest intracellular indicator of LR asymmetry establishment.I hypothesize that endoderm cells regulate LR determination in two ways: regulating node formation and/or function and transferring LR signal from the node to the LPM. We are testing this hypothesis by analyzing Sox17 mutants to determine the cause(s) of their LR asymmetry defects. This is an especially useful context in which to study the role of endoderm in LR determination because Sox17 is expressed only in the endoderm cells at the time LR asymmetry is established in the node; however&s_comma; Sox17 mutants develop LR asymmetry defects as well. In particular&s_comma; we found that Sox17 null mutants show no _expression of Nodal in the LPM&s_comma; even though the LPM is otherwise normal. This suggests that the early steps in LR determination are defective in Sox17 mutants due to dysfunction of the endoderm.I will discuss the roles of endoderm cells in LR determination.

問い合わせ先:  東京大学 獣医解剖 (03-5841-5384)