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Development ; 132(24): 5425-36, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16291790

RESUMO

The alignment of the left-right (LR) body axis relative to the anteroposterior (AP) and dorsoventral (DV) axes is central to the organization of the vertebrate body plan and is controlled by the node/organizer. Somitogenesis plays a key role in embryo morphogenesis as a principal component of AP elongation. How morphogenesis is coupled to axis specification is not well understood. We demonstrate that Wnt3a is required for LR asymmetry. Wnt3a activates the Delta/Notch pathway to regulate perinodal expression of the left determinant Nodal, while simultaneously controlling the segmentation clock and the molecular oscillations of the Wnt/beta-catenin and Notch pathways. We provide evidence that Wnt3a, expressed in the primitive streak and dorsal posterior node, acts as a long-range signaling molecule, directly regulating target gene expression throughout the node and presomitic mesoderm. Wnt3a may also modulate the symmetry-breaking activity of mechanosensory cilia in the node. Thus, Wnt3a links the segmentation clock and AP axis elongation with key left-determining events, suggesting that Wnt3a is an integral component of the trunk organizer.


Assuntos
Padronização Corporal , Somitos/fisiologia , Proteínas Wnt/fisiologia , Animais , Cílios/fisiologia , Embrião de Mamíferos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Transgênicos , Morfogênese , Mutação , Proteína Nodal , Receptores Notch/metabolismo , Canais de Cátion TRPP/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/genética , Proteína Wnt3 , Proteína Wnt3A , beta Catenina/metabolismo
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