TY - JOUR
T1 - Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling
AU - Taniguchi, Koji
AU - Ayada, Toranoshin
AU - Ichiyama, Kenji
AU - Kohno, Ri ichiro
AU - Yonemitsu, Yoshikazu
AU - Minami, Yasuhiro
AU - Kikuchi, Akira
AU - Maehara, Yoshihiko
AU - Yoshimura, Akihiko
N1 - Funding Information:
We thank T. Yoshioka, H. Fujii, N. Kinoshita, M. Ohtsu, Y. Yamada for technical assistance, and Ms. Y. Nishi for manuscript preparation. This work was supported by special Grants-in-aid from the Ministry of Education, Science, Technology, Sports, and Culture of Japan.
PY - 2007/1/26
Y1 - 2007/1/26
N2 - Sprouty genes encode cytoplasmic membrane-associated proteins that inhibit receptor tyrosine kinase signaling. Four orthologs of Drosophila Sprouty (dSpry) (Sprouty1-4) have been identified in mammals. Physiological function of Sprouty1 and Sprouty2 has been investigated using gene targeting approaches, however to date detailed examination of Sprouty4 knockout (KO) mice has not been reported. In this study, Sprouty4 KO mice were generated and characterized. Although a significant fraction of Sprouty4 KO mice died shortly after birth due to mandible defects, the remainder were viable and fertile. Growth retardation was observed for most Sprouty4-deficient mice, with nearly all Sprouty4 KO mice having polysyndactyly. ERK activation was sustained in Sprouty4 KO mouse embryonic fibroblasts (MEFs) in response to FGF, but not to EGF. Sprouty2 and Sprouty4 double KO (DKO) mice were embryonic lethal and showed severe defects in craniofacial, limb, and lung morphogenesis. These findings suggest both redundant and non-redundant functions for Sprouty2 and Sprouty4 on embryonic development and FGF signaling.
AB - Sprouty genes encode cytoplasmic membrane-associated proteins that inhibit receptor tyrosine kinase signaling. Four orthologs of Drosophila Sprouty (dSpry) (Sprouty1-4) have been identified in mammals. Physiological function of Sprouty1 and Sprouty2 has been investigated using gene targeting approaches, however to date detailed examination of Sprouty4 knockout (KO) mice has not been reported. In this study, Sprouty4 KO mice were generated and characterized. Although a significant fraction of Sprouty4 KO mice died shortly after birth due to mandible defects, the remainder were viable and fertile. Growth retardation was observed for most Sprouty4-deficient mice, with nearly all Sprouty4 KO mice having polysyndactyly. ERK activation was sustained in Sprouty4 KO mouse embryonic fibroblasts (MEFs) in response to FGF, but not to EGF. Sprouty2 and Sprouty4 double KO (DKO) mice were embryonic lethal and showed severe defects in craniofacial, limb, and lung morphogenesis. These findings suggest both redundant and non-redundant functions for Sprouty2 and Sprouty4 on embryonic development and FGF signaling.
KW - Embryonic development
KW - FGF
KW - Knockout mouse
KW - Negative regulation
KW - Signal transduction
KW - Sprouty
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U2 - 10.1016/j.bbrc.2006.11.107
DO - 10.1016/j.bbrc.2006.11.107
M3 - Article
C2 - 17156747
AN - SCOPUS:33845412960
SN - 0006-291X
VL - 352
SP - 896
EP - 902
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -