2004 Fiscal Year Final Research Report Summary
In vitro inducion of pituitary cell lineage in mammalian.
| Project/Area Number |
14571531
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
TAKUMA Naoyuki Asahikawa Medical College, Obstetrics and Gynecology, Associate Professor, 医学部, 助教授 (10312464)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Tsuyoshi Asahikawa Medical College, Obstetrics and Gynecology, Assistant Professor, 医学部, 講師 (30271787)
SENGOKU Kazuo Asahikawa Medical College, Obstetrics and Gynecology, Professor, 医学部, 教授 (30163124)
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| Project Period (FY) |
2002 – 2004
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| Keywords | SHH / BMP4 / FGF8 / Lhx3 / Lhx4 / Isl1 / oral ectoderm / Rathke's pouch |
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| Research Abstract |
Nkx2.1 (T/ebp, Ttf1, Titf1) is a homeobox gene expressed in the ventral diencephalon during forebrain formation that is not expressed in Rathke's pouch or in the pituitary gland at any time of embryogenesis. However, targeted mutation of this gene in mice results in ablation of the pituitary. Examination of pituitary development in Nkx2.1 homozygous null mutant embryos revealed that a pouch rudiment is initially formed, but is eliminated before formation of a definitive pouch. In the diencephalon of the mutant, Bmp4 expression is maintained, whereas Fgf8 expression is not detectable. These data, together with previously published genetic and molecular observations, suggest that Rathke's pouch develops in a two step process that requires at least two sequential inductive signals from the diencephalon. BMP4 is required for induction and formation of the pouch rudiment, a role confirmed by analysis of Bmp4 homozygous null mutant embryos. FGF8 is necessary for activation of the key regulatory gene Lhx3 and subsequent development of the pouch rudiment into a definitive pouch. Moreover, SHH signal from oral ectoderm is required for activation of Nkx2.1. In vitro culture, the oral ectoderm, however, fails to differentiate further. It remains single layered, and is subsequently eliminated through programmed cell death at mouse E11.5 embryonic day. In this study we also describe the cloning and expression patterns of a novel gene encoding a protein containing a His-Thr domain, Spot-2. Spot-2 is exclusively expressed in the pituitary from stage E13.5 to E15.5. Mouse Lhx3 plays a critical role during early organogenesis in the pituitary. The Spot-2 gene appears to be a downstream gene of Lhx3. It is suggested that Spot-2 plays important roles in pituitary development.
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