Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling.
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.
Taniguchi
Koji
K
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Ayada
Toranoshin
T
Ichiyama
Kenji
K
Kohno
Ri-Ichiro
R
Yonemitsu
Yoshikazu
Y
Minami
Yasuhiro
Y
Kikuchi
Akira
A
Maehara
Yoshihiko
Y
Yoshimura
Akihiko
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D046509:Tissue Culture Techniques
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C499037:Spry4 protein, mouse; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse