Molecular mechanisms of thyroid C-cell differentiation using gene targeting mice.
| Project/Area Number |
17590174
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Kitasato University |
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Principal Investigator |
KAMEDA Yoko Kitasato University, School of Medicine Department of Anatomy, Professor, 医学部, 教授 (10032898)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Masaaki Kitasato University, School of Medicine Department of Anatomy, Assistant Professor, 医学部, 講師 (60276053)
ARAI Yuta Kitasato University, School of Medicine Department of Anatomy, Assistant Professor, 医学部, 講師 (60329026)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Gene targeting mice / Development / Thyroid C cells / E-Cadherin / Endodermal origin / Ultimobranchial body / Mash1 / Molecular mechanism / 鯛後体 / 遺伝子 / MeuroD |
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| Research Abstract |
The bHLH transcription factor Mash1 plays a key role in the differentiation of autonomic neurons from neural crest cells. Mash1 null mutant mice lack sympathetic ganglion, olfactory receptor neurons, lung neuroendocrine cells and carotid body glomus cells. Thyroid C cells synthesize and secrete serum calcium-lowering hormone, calcitonin. The ultimobranchial body derived from the fourth pharyngeal pouch enters the thyroid gland to become C cells. To clarify the molecular mechanisms involved in the differentiation of C cells from their ultimobranchial progenitors, the present study examined the development of ultimobranchial body and C cells in Mash1 null mutant embryos and neonates, in comparison with wild types. Thyroid C cells of newborn mice are immunoreactive for CGRP, PGP9. 5, and NeuroD, and transiently exhibit the neuronal markers Tun. and somatostatin during fetal development. Mash1 is expressed at embryonic day (E) 12.5 in the ultimobranchial body and also in the organ fused wi
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th the thyroid lobe at E 13.5. Targeted disruption of Mash1 resulted in the absence of C cells in the mouse thyroid glands. While the formation and migration of the ultimobranchial body were not affected in the Mash1 null mutants, at E12.5-E13.5 both the ultimobranchial body and the organ populating the thyroid lobe exhibited a marked increase in apoptotic cell numbers. Thus, in the mutant mice, the ultimobranchial body fails to complete its differentiation program and finally dies. These results indicate that the Mash1-dependent signaling pathway plays an important role in C-cell development. During the organogenesis, the ultimobranchial bodies were not colonized by the neural crest cells. On the other hand, all ultimobranchial cells, as well as the epithelium of the fourth pharyngeal pouch were intensely immunoreactive for E-cadherin, an epithelial marker. Furthermore, in newborn mouse thyroid glands the colocalization of calcitonin and E-cadherin was confirmed by confocal microscopy. Thus, the mouse thyroid C cells are derived from the endodermal epithelial cells of the fourth pharyngeal pouch and are not from the neural crest cells. Mash1 may induce the neuronal traits in C cells derived from the endoderm. Less
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Report
(3 results)
Research Products
(17 results)
