TY - JOUR
T1 - Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis
AU - Aoto, Kazushi
AU - Shikata, Yayoi
AU - Imai, Hajime
AU - Matsumaru, Daisuke
AU - Tokunaga, Tomoyuki
AU - Shioda, Seiji
AU - Yamada, Gen
AU - Motoyama, Jun
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell fate mapping
KW - Gli3
KW - Holoprosencephaly
KW - Prechordal mesoderm
KW - Prechordal plate
KW - Sonic hedgehog (Shh)
KW - Ventral cranial mesoderm
UR - http://www.scopus.com/inward/record.url?scp=59649089246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649089246&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2008.11.022
DO - 10.1016/j.ydbio.2008.11.022
M3 - Article
C2 - 19103193
AN - SCOPUS:59649089246
VL - 327
SP - 106
EP - 120
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -