RESUMO
Semaphorin 3C is a secreted member of the semaphorin gene family. To investigate its function in vivo, we have disrupted the semaphorin 3C locus in mice by targeted mutagenesis. semaphorin 3C mutant mice die within hours after birth from congenital cardiovascular defects consisting of interruption of the aortic arch and improper septation of the cardiac outflow tract. This phenotype is similar to that reported following ablation of the cardiac neural crest in chick embryos and resembles congenital heart defects seen in humans. Semaphorin 3C is expressed in the cardiac outflow tract as neural crest cells migrate into it. Their entry is disrupted in semaphorin 3C mutant mice. These data suggest that semaphorin 3C promotes crest cell migration into the proximal cardiac outflow tract.
Assuntos
Aorta Torácica/anormalidades , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Semaforina-3A , Tronco Arterial/química , Proteínas de Peixe-Zebra/agonistas , Sequência de Aminoácidos , Animais , Genótipo , Hibridização In Situ , Integrases/metabolismo , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação , Fenótipo , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Recombinação Genética , Retinal Desidrogenase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fatores de Tempo , Proteínas Virais/metabolismoRESUMO
Transcript localizations for Mox genes have implicated this homeobox gene subfamily in the early steps of mesoderm formation. We have extended these studies by determining the protein expression profile of Mox-1 and Mox-2 during mouse development. The time of onset of Mox protein expression has been accurately obtained to provide clues as to their roles during gastrulation. Expression of Mox-1 protein is first detected in the newly formed mesoderm of primitive streak stage mouse embryos (7.5 days post-coitum, d.p.c.). In contrast, Mox-2 protein is first detected at 9.0 d.p.c. in thr already formed somites. Additionally, immunostaining reveals new and distinct areas of Mox expression in the branchial arches and limbs that were not reported in our previous mRNA localization analysis. Mouse Mox-2 antibodies cross-react specifically in similar embryonic tissues in chick indicating the conservation of function of Mox genes in vertebrates. These expression data suggest that the Mox genes function transiently in the formation of mesodermal and mesenchymal derivatives, after their initial specification, but before their overt differentiation. Furthermore, while there appears to be some overlap in protein expression between Mox-1 and Mox-2 during somitogenesis, unique areas of expression indicate several distinct roles for the Mox genes during development.
