Rac1 is essential for basement membrane-dependent epiblast survival
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Rac1 is essential for basement membrane-dependent epiblast survival. / He, Xiaowen; Liu, Jie; Qi, Yanmei; Brakebusch, Cord; Chrostek-Grashoff, Anna; Edgar, David; Yurchenco, Peter D; Corbett, Siobhan A; Lowry, Stephen F; Graham, Alan M; Han, Yaling; Li, Shaohua.
In: Molecular and Cellular Biology, Vol. 30, No. 14, 2010, p. 3569-81.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rac1 is essential for basement membrane-dependent epiblast survival
AU - He, Xiaowen
AU - Liu, Jie
AU - Qi, Yanmei
AU - Brakebusch, Cord
AU - Chrostek-Grashoff, Anna
AU - Edgar, David
AU - Yurchenco, Peter D
AU - Corbett, Siobhan A
AU - Lowry, Stephen F
AU - Graham, Alan M
AU - Han, Yaling
AU - Li, Shaohua
N1 - Keywords: 1-Phosphatidylinositol 3-Kinase; Animals; Antigens, CD29; Apoptosis; Basement Membrane; Cell Line; Cell Survival; Embryonic Development; Embryonic Stem Cells; Epithelium; Germ Layers; Guanine Nucleotide Exchange Factors; Mice; Neuropeptides; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-crk; Recombinant Proteins; Signal Transduction; rac GTP-Binding Proteins
PY - 2010
Y1 - 2010
N2 - During murine peri-implantation development, the egg cylinder forms from a solid cell mass by the apoptotic removal of inner cells that do not contact the basement membrane (BM) and the selective survival of the epiblast epithelium, which does. The signaling pathways that mediate this fundamental biological process are largely unknown. Here we demonstrate that Rac1 ablation in embryonic stem cell-derived embryoid bodies (EBs) leads to massive apoptosis of epiblast cells in contact with the BM. Expression of wild-type Rac1 in the mutant EBs rescues the BM-contacting epiblast, while expression of a constitutively active Rac1 additionally blocks the apoptosis of inner cells and cavitation, indicating that the spatially regulated activation of Rac1 is required for epithelial cyst formation. We further show that Rac1 is activated through integrin-mediated recruitment of the Crk-DOCK180 complex and mediates BM-dependent epiblast survival through activating the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. Our results reveal a signaling cascade triggered by cell-BM interactions essential for epithelial morphogenesis.
AB - During murine peri-implantation development, the egg cylinder forms from a solid cell mass by the apoptotic removal of inner cells that do not contact the basement membrane (BM) and the selective survival of the epiblast epithelium, which does. The signaling pathways that mediate this fundamental biological process are largely unknown. Here we demonstrate that Rac1 ablation in embryonic stem cell-derived embryoid bodies (EBs) leads to massive apoptosis of epiblast cells in contact with the BM. Expression of wild-type Rac1 in the mutant EBs rescues the BM-contacting epiblast, while expression of a constitutively active Rac1 additionally blocks the apoptosis of inner cells and cavitation, indicating that the spatially regulated activation of Rac1 is required for epithelial cyst formation. We further show that Rac1 is activated through integrin-mediated recruitment of the Crk-DOCK180 complex and mediates BM-dependent epiblast survival through activating the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. Our results reveal a signaling cascade triggered by cell-BM interactions essential for epithelial morphogenesis.
U2 - 10.1128/MCB.01366-09
DO - 10.1128/MCB.01366-09
M3 - Journal article
C2 - 20457815
VL - 30
SP - 3569
EP - 3581
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 14
ER -
ID: 21664101