2007 Fiscal Year Final Research Report Summary
Molecular mechanism that controls early morphogenesis of the vertebrate respiratory system
Project/Area Number |
16207015
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Developmental biology
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Research Institution | Nagoya University |
Principal Investigator |
KUROIWA Atsushi Nagoya University, Graduate school of Science, professor (20134611)
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Project Period (FY) |
2004 – 2007
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Keywords | Hox gene / digestive-respiratory system / Fgf10 / dorsoventral polarity / transcriptional control / enhancer / microarray / transgenic mouse |
Research Abstract |
(1) The expression domain of Fgf10 become restricted the mesoderm lining the endodermal protruding of the primary bronchus. This restriction takes place at the anterior expression boundary of graded Hoxb-6 expression domain. From gain-and loss-of-function experiment, we found that ectopic Fgf10 expression was induced at both side of the Hoxb-6 expression boundary. This indicates that Fgf10 expression is induced by Hoxb-6 dependent cell to tell communication. Actuary we found that Hoxb-6 represses EphA4 expression and activates efnb1 expression. Ectopic EphA4 or efnb1 expression induces Fgf10 expression at their expression boundary, indicating that these molecules are involved in the Fgf10 expression. In addition, we found that the expression boundary of Hoxb-6 has a role of the signaling center and induces the paired morphogenesis of the primary bronchus at the posterior region of the respiratory anlagen. (2) We tried to identify the lung specific enhancer of Fgf10 gene by transgenic mouse system. We found that the multiple lung specific enhancers are present in the introngenic 7kb DNA that also carries the limb bud specific enhancer. The lung specific enhancers cooperate each other with the sequence present in the Fgf10 promoter and/or 5' upstream sequence for lung specific expression. (3) We tried to identify the genes that are specifically expressed in the lung anlagen by microarray analysis followed by WISH. We found that transcription factors potentially involved in the control of Fgf10, for example Isl1 and Tbx20, are identified as a candidate gene. Interestingly, majority of these genes are also expressed in the heart, indicating that similar mechanism is present for induction both heart and lung anlagen at early development. Wnt2 expression was found from very early in the lung anlagen, indicating the involvement of Fgf10 expression through Wnt/beta-catenin system.
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Research Products
(27 results)
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[Journal Article] Forgut endoderm is specified early in avian development through signal(s) emanating from Hensen's node or its derivatives.2008
Author(s)
Matsushita, S., Urase, K., Komatsu, A., Scotting, P. J., Kuroiwa, A., Yasugi, S.
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Journal Title
Mech. Dev. 125
Pages: 377-395
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular genetic cascades for external genitalia formation- an emerging organogenesis program.2006
Author(s)
Yamada, G., Suzuki, K., Haraguchi, R., Miyagawa, S., Satoh, Y, Kamimura, M., Nakagata, N., Kataoka, H., Kuroiwa, A., Chen, Y.
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Journal Title
Dev. Dyn. 235
Pages: 1738-1752
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crucial transcription factors in endoderm and embryonic gut development are expressed in gut-like structures from mouse ES cells.2005
Author(s)
Matsuura, R., Kogo, H., Ogaeri, T., Miwa, T., M., K., Kanai, Y, Nakagawa, T., Kuroiwa, A., Fujimoto, T. Torihashi, S.
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Journal Title
Stem Cells 24
Pages: 624-30
Description
「研究成果報告書概要(欧文)」より
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