RESUMO
Asymmetric expression of Sonic hedgehog (Shh) in Hensen's node of the chicken embryo plays a key role in the genetic cascade that controls left-right asymmetry, but its involvement in left-right specification in other vertebrates remains unclear. We show that mouse embryos lacking Shh display a variety of laterality defects, including pulmonary left isomerism, alterations of heart looping, and randomization of axial turning. Expression of the left-specific gene Lefty-1 is absent in Shh(-/-) embryos, suggesting that the observed laterality defects could be the result of the lack of Lefty-1. We also demonstrate that retinoic acid (RA) controls Lefty-1 expression in a pathway downstream or parallel to Shh. Further, we provide evidence that RA controls left-right development across vertebrate species. Thus, the roles of Shh and RA in left-right specification indeed are conserved among vertebrates, and the Shh and RA pathways converge in the control of Lefty-1.
Assuntos
Anormalidades Congênitas/etiologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas/fisiologia , Transativadores , Fator de Crescimento Transformador beta/genética , Tretinoína/fisiologia , Animais , Sequência de Bases , Embrião de Galinha , Proteínas Hedgehog , Fatores de Determinação Direita-Esquerda , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , RNA Mensageiro/análiseRESUMO
During embryonic development, initially similar fields can develop into distinct structures, such as the vertebrate fore- and hindlimbs. Although considerable progress has been made in our understanding of the genetic control underlying the establishment of the different limb axes, the molecular cues that specify the differential development of the fore- and hindlimbs are unknown. Possible candidates for genes determining limb identity are Pitx1, a gene whose transcripts are detected in the early hind- but not forelimb bud, and two members of the T-box (Tbx) gene family, Tbx4 and Tbx5, which are specifically expressed in the hindlimb and forelimb buds, respectively. Here we show that Tbx4 and Tbx5 are essential regulators of limb outgrowth whose roles seem to be tightly linked to the activity of three signalling proteins that are required for limb outgrowth and patterning: fibroblast growth factor (FGF), bone morphogenetic protein (BMP) and Wnt. In addition, we provide evidence that Tbx4 and Tbx5 are involved in controlling limb identity. Our findings provide insight into how similar developmental fields can evolve into homologous but distinct structures.
Assuntos
Proteínas Aviárias , Desenvolvimento Embrionário , Proteínas com Domínio T , Fatores de Transcrição/genética , Proteínas de Peixe-Zebra , Animais , Proteínas Morfogenéticas Ósseas/fisiologia , Embrião de Galinha , Embrião não Mamífero/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Membro Anterior/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Membro Posterior/embriologia , Botões de Extremidades/embriologia , Morfogênese/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Transdução de Sinais , Fatores de Transcrição/fisiologia , Proteínas WntRESUMO
apterous specifies dorsal cell fate and directs outgrowth of the wing during Drosophila wing development. Here we show that, in vertebrates, these functions appear to be performed by two separate proteins. Lmx-1 is necessary and sufficient to specify dorsal identity and Lhx2 regulates limb outgrowth. Our results suggest that Lhx2 is closer to apterous than Lmx-1, yet, in vertebrates, Lhx2 does not specify dorsal cell fate. This implies that in vertebrates, unlike Drosophila, limb outgrowth can be dissociated from the establishment of the dorsoventral axis.
