RESUMO
The cerebellum develops from the rhombic lip of the rostral hindbrain and is organized by fibroblast growth factor 8 (FGF8) expressed by the isthmus. Here we report characterization of Irx2, a member of the Iroquois (Iro) and Irx class of homeobox genes, that is expressed in the presumptive cerebellum. When Irx2 is misexpressed with Fgf8a in the chick midbrain, the midbrain develops into cerebellum in conjunction with repression of Otx2 and induction of Gbx2. During this event, signaling by the FGF8 and mitogen-activated protein (MAP) kinase cascade modulates the activity of Irx2 by phosphorylation. Our data identify a link between the isthmic organizer and Irx2, thereby shedding light on the roles of Iro and Irx genes, which are conserved in both vertebrates and invertebrates.
Assuntos
Cerebelo/embriologia , Cerebelo/metabolismo , Fatores de Crescimento de Fibroblastos/biossíntese , Proteínas de Homeodomínio/biossíntese , Sistema de Sinalização das MAP Quinases/fisiologia , Fatores de Transcrição/biossíntese , Animais , Células COS , Embrião de Galinha , Chlorocebus aethiops , Fator 8 de Crescimento de Fibroblasto , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Homeodomínio/genética , Camundongos , Fatores de Transcrição/genéticaRESUMO
Msx1 and Msx2 genes encode the homeodomain transcription factors. Several gene knockout mice and expression studies suggest that they possess functionally redundant roles in embryogenesis. In this study, we revealed that Msx1 and Msx2 were expressed during ventral body wall formation in an overlapping manner. Msx1/Msx2 double-mutant mice displayed embryonic abdominal wall defects with disorganized muscle layers and connective tissues. These findings indicate that Msx1 and Msx2 play roles in concert during embryonic ventral abdominal wall formation.
Assuntos
Músculos Abdominais/anormalidades , Parede Abdominal/anormalidades , Proteínas de Ligação a DNA/genética , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Músculos Abdominais/metabolismo , Músculos Abdominais/patologia , Parede Abdominal/patologia , Animais , Proteínas de Ligação a DNA/metabolismo , Feminino , Predisposição Genética para Doença , Hérnia Abdominal/congênito , Hérnia Abdominal/genética , Proteínas de Homeodomínio/metabolismo , Hibridização In Situ , Fator de Transcrição MSX1 , Masculino , Camundongos , Camundongos KnockoutAssuntos
Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/fisiologia , Camundongos Knockout , Animais , Sistema Nervoso Central/embriologia , Condrogênese/genética , Epiderme/embriologia , Camundongos , Músculo Esquelético/fisiologia , Organogênese/genética , Osteogênese/genética , Regeneração/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
In vertebrates and invertebrates, BMP/Dpp (Bone Morphogenetic Protein/Decapentaplegic) signaling regulates the orchestrated processes of embryogenesis. Recent studies have revealed that BMP/Dpp signaling is controlled extracellularly as well as intracellularly. One extracellular regulatory molecule is the Chordin/Short gastrulation protein (Chordin/Sog), a secreted protein that acts as an antagonist to BMP/Dpp. Chordin/Sog contains four cysteine-rich (CR) domains that bind to and inactivate BMP/Dpp. In contrast, a positive regulator has been identified in Drosophila. Named crossveinless 2 (cv-2), this molecule contains five CR domains at the N-terminal half and a von Willebrand factor D domain at the C-terminal part. Genetic data suggest that Cv-2 potentiates Dpp signaling. We isolated chick and mouse CV-2 genes and found that CV-2 is secreted and enhances BMP signaling. Expression patterns were closely related to those of BMPs, supporting the likelihood of a tight link. Our data show for the first time that CV-2 is a conserved, positive regulator of BMP signaling and that CR domain proteins act as both positive and negative modulators of BMP signaling.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Vertebrados/embriologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Embrião de Galinha , Sequência Conservada , Cisteína/química , Proteínas de Drosophila/química , Desenvolvimento Embrionário , Glicoproteínas/química , Glicoproteínas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Proteínas de Insetos/química , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Transdução de Sinais/genética , Fator de von Willebrand/químicaRESUMO
A tight loop between members of the fibroblast growth factor and the Wnt families plays a key role in the initiation of vertebrate limb development. We show for the first time that Tbx5 and Tbx4 are directly involved in this process. When dominant-negative forms of these Tbx genes were misexpressed in the chick prospective limb fields, a limbless phenotype arose with repression of both Wnt and Fgf genes By contrast, when Tbx5 and Tbx4 were misexpressed in the flank, an additional wing-like and an additional leg-like limbs were induced, respectively. This additional limb formation was accompanied by the induction of both Wnt and Fgf genes These results highlight the pivotal roles of Tbx5 and Tbx4 during limb initiation, specification of forelimb/hindlimb and evolution of tetrapod limbs, placing Tbx genes at the center of a highly conserved genetic program.