Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis

Kazushi Aoto, Yayoi Shikata, Hajime Imai, Daisuke Matsumaru, Tomoyuki Tokunaga, Seiji Shioda, Gen Yamada, Jun Motoyama

研究成果: Article

53 引用 (Scopus)

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In humans, holoprosencephaly (HPE) is a common birth defect characterized by the absence of midline cells from brain, facial, and oral structures. To understand the pathoetiology of HPE, we investigated the involvement of mammalian prechordal plate (PrCP) cells in HPE pathogenesis and the requirement of the secreted protein sonic hedgehog (Shh) in PrCP development. We show using rat PrCP lesion experiments and DiI labeling that PrCP cells are essential for midline development of the forebrain, foregut endoderm, and ventral cranial mesoderm in mammals. We demonstrate that PrCP cells do not develop into ventral cranial mesoderm in Shh-/- embryos. Using Shh-/- and chimeric embryos we show that Shh signal is required for the maintenance of PrCP cells in a non-cell autonomous manner. In addition, the hedgehog (HH)-responding cells that normally appear during PrCP development to contribute to midline tissues, do not develop in the absence of Shh signaling. This suggests that Shh protein secreted from PrCP cells induces the differentiation of HH-responding cells into midline cells. In the present study, we show that the maintenance of a viable population of PrCP cells by Shh signal is an essential process in development of the midline of the brain and craniofacial structures. These findings provide new insight into the mechanism underlying HPE pathoetiology during dynamic brain and craniofacial morphogenesis.

元の言語English
ページ(範囲)106-120
ページ数15
ジャーナルDevelopmental Biology
327
発行部数1
DOI
出版物ステータスPublished - 2009 3 1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Aoto, K., Shikata, Y., Imai, H., Matsumaru, D., Tokunaga, T., Shioda, S., Yamada, G., & Motoyama, J. (2009). Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis. Developmental Biology, 327(1), 106-120. https://doi.org/10.1016/j.ydbio.2008.11.022