RESUMO
The canonical Wnt/ß-catenin pathway is an essential component of multiple developmental processes. To investigate the role of this pathway in the ectoderm during facial morphogenesis, we generated conditional ß-catenin mouse mutants using a novel ectoderm-specific Cre recombinase transgenic line. Our results demonstrate that ablating or stabilizing ß-catenin in the embryonic ectoderm causes dramatic changes in facial morphology. There are accompanying alterations in the expression of Fgf8 and Shh, key molecules that establish a signaling center critical for facial patterning, the frontonasal ectodermal zone (FEZ). These data indicate that Wnt/ß-catenin signaling within the ectoderm is critical for facial development and further suggest that this pathway is an important mechanism for generating the diverse facial shapes of vertebrates during evolution.
Assuntos
Ectoderma/fisiologia , Ossos Faciais/embriologia , Morfogênese/fisiologia , Transdução de Sinais/fisiologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Primers do DNA/genética , Ectoderma/metabolismo , Ossos Faciais/ultraestrutura , Fator 4 de Crescimento de Fibroblastos/metabolismo , Fator 8 de Crescimento de Fibroblasto/metabolismo , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica de Varredura , Reação em Cadeia da Polimerase , beta Catenina/genéticaRESUMO
Previous studies identified Inka1 as a gene regulated by AP-2alpha in the neural crest required for craniofacial morphogenesis in fish and frog. Here, we extend the analysis of Inka1 function and regulation to the mouse by generating a LacZ knock-in allele. Inka1-LacZ allele expression occurs in the cephalic mesenchyme, heart, and paraxial mesoderm prior to E8.5. Subsequently, expression is observed in the migratory neural crest cells and their derivatives. Consistent with expression of Inka1 in tissues of the developing head during neurulation, a low percentage of Inka1(-/-) mice show exencephaly while the remainder are viable and fertile. Further studies indicate that AP-2alpha is not required for Inka1 expression in the mouse, and suggest that there is no significant genetic interaction between these two factors during embryogenesis. Together, these data demonstrate that while the expression domain of Inka1 is conserved among vertebrates, its function and regulation are not.
