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理化学研究所 横浜研究所 免疫・アレルギー科学総合研究センターでは以下のセミナーを行います。

場所:理化学研究所 横浜研究所 北研究棟 RCAI 6階 大セミナー室

講師:Dr. G.A. Holländer (Professor of Molecular Medicine in Paediatrics&s_comma;
University of Basel)

演題: Cellular and molecular aspects of thymus development

The thymus serves as the only primary lymphoid organ for the generation of
mature T cells that bear an antigen-receptor able to recognize harmful
foreign antigens but unable to respond to beneficial self-antigens. This
unique ability to select a functionally competent repertoire of T cells is
dependent on the presence&s_comma; the regular composition and the normal
architectural organization of thymic stromal cells. The cellular compartment
is composed of epithelial cells and non-epithelial cells (i.e. fibroblasts&s_comma;
makrophages&s_comma; indigitating reticular cells&s_comma; etc.) that create distinct
microenvironments. The bi-directional physical and functional interaction
between lymphoid and stromal cells allows for the mutual maturation of both
cellular compartments leading ultimately to the generation of a normal
thymic stroma and the regular differentiation and selection of functionally
competent T cells.
Epithelial cells of the ventral aspects of the third pharyngeal pouch
endoderm and mesenchymal cells derived from both the autochtoneous mesoderm
of the surrounding pharyngeal arches and from immigrating neural crest cells
provide the precursor cells necessary for the formation of a regular thymus
anlage. While the cellular origins of the thymic primordium are now well
established&s_comma; it is the precise molecular nature of the inductive signals
that are not yet defined. Different approaches have been taken to elucidate
the genetic programs regulating thymic organogenesis. The analysis of
spontaneous mutants and animals rendered deficient for specific genes have
revealed that both mesenchymal stromal cells and lymphoid cells committed to
a intrathymic development influence the growth and differentiation of the
thymic epithelial compartment during early stages of organogenesis. However&s_comma;
the precise molecular mechanisms by which the lack of specific components of
signaling pathways or the absence of a specific morphogen prevent the
commitment to and the expansion of thymic epithelial cells&s_comma; respectively&s_comma;
remains still largely unknown.
Data will be presented demonstrating that endodermal epithelial cells acting
as precursors for the thymus primordium express receptors for signaling via
Wnt molecules&s_comma; fibroblast growth factors&s_comma; sonic hedgehog&s_comma; and several
members of the extended familiy of TGF-b molecules. Indeed&s_comma; signaling
pathways that are (i) specifically activated by Wnt glycoproteins&s_comma; hedgehog
proteins as well as TGF-b family members and (ii) known to be implicated in
mesenchymal-epithelial cell induction appear to be directly involved in
thymus organogenesis.

免疫発生研究チーム  チームリーダー
河本 宏
045-503-7010 (内6641)
045-503-7011 (内6642) (秘書・研究員室) e-mail: kawamoto@rcai.riken.jp

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