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First published online October 6, 2005
Stem Cells Vol. 24 No. 3 March 2006, pp. 624 -630
doi:10.1634/stemcells.2005-0344; www.StemCells.com
© 2006 AlphaMed Press

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EMBRYONIC STEM CELLS

Crucial Transcription Factors in Endoderm and Embryonic Gut Development Are Expressed in Gut-Like Structures from Mouse ES Cells

Rie Matsuuraa, Hiroshi Kogoa, Takunori Ogaeria, Takashi Miwaa, Masaki Kuwaharaa, Yoshiakira Kanaic, Takumi Nakagawab, Atsushi Kuroiwab, Toyoshi Fujimotoa, Shigeko Torihashia

a Department of Anatomy and Molecular Cell Biology, Graduate School of Medicine, and
b Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan;
c Department of Anatomy, Graduate School of Agriculture and Life Science, University of Tokyo, Tokyo, Japan

Key Words. Embryonic stem cell • Embryoid body • Transcription factors • Development • Gastrointestinal motility

Correspondence: Shigeko Torihashi, Ph.D., Department of Health Science, Nagoya University Graduate School of Medicine, 1-1-20 Daikouminami, Higashi-ku Nagoya 461-8673, Japan. Telephone: 81-52-719-1344; Fax: 81-52-719-1344; e-mail: storiha{at}med.nagoya-u.ac.jp

Received July 28, 2005; accepted for publication September 27, 2005.
Mouse embryonic stem (ES) cells are pluripotent and retain the potential to form an organ similar to the gut showing spontaneous contractions in vitro. The morphological features of these structures and their formation, as assessed using the hanging drop method to produce embryoid bodies (EBs), seem to be similar to those in vivo. To determine whether the same molecular mechanisms are involved in the formation process, the expression pattern of transcription factors regulating endoderm and gut development in the mouse embryo was examined by in situ hybridization and compared with in vivo expression. Expression of gene products was also examined by immunohistochemistry, and expression colocalization was analyzed with double staining. The results showed that all factors examined, that is, Sox17, Id2, HNF3ß/Foxa2, and GATA4, were expressed in both EBs and gut-like structures. Moreover, their expression patterns were similar to those in the mouse embryo. EBs after the hanging drop period and before outgrowth already expressed all factors that were colocalized with each other in EB epithelial structures. These findings suggest that the origin of the gut-like structure is determined during the hanging drop period and that the gut-like structure is formed as the epithelial structure in EBs during the hanging drop period. They also indicate that the in vitro system using mouse ES cells mimics in vivo development and should prove useful in the study of molecular mechanisms for endoderm and gut development.




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S. Torihashi, M. Kuwahara, T. Ogaeri, P. Zhu, M. Kurahashi, and T. Fujimoto
Gut-Like Structures from Mouse Embryonic Stem Cells as an In Vitro Model for Gut Organogenesis Preserving Developmental Potential After Transplantation
Stem Cells, December 1, 2006; 24(12): 2618 - 2626.
[Abstract] [Full Text] [PDF]




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