Assuntos
DNA Helicases/genética , Ceratose , Esclerodermia Localizada , Neoplasias Cutâneas , Feminino , Humanos , Masculino , Linhagem , Isoformas de ProteínasRESUMO
Matthew-Wood syndrome (MWS), also termed Microphthalmia, syndrome 9 (MCOPS9, MIM 601186), Spear syndrome, or pulmonary hypoplasia, diaphragmatic hernia, anophthalmia and cardiac defects syndrome (PDAC syndrome), is an autosomal recessive disorder characterised by ocular, respiratory and cardiac abnormalities. Mutations in retinoic acid 6 gene (STRA6) have been reported in clinically diagnosed patients with MWS. Here we presented a case with MWS, who has characteristic findings of the syndrome as well as dextrocardia as an undescribed feature, and bilateral streak gonads which was described only in one patient previously. Molecular analysis showed a homozygous exonic missense mutation in the STRA6 gene.
Assuntos
Anoftalmia/genética , Dextrocardia/genética , Disgenesia Gonadal/genética , Pneumopatias/genética , Proteínas de Membrana/genética , Microftalmia/genética , Mutação de Sentido Incorreto/genética , Anoftalmia/diagnóstico , Consanguinidade , Dextrocardia/diagnóstico , Éxons/genética , Feminino , Disgenesia Gonadal/diagnóstico , Homozigoto , Humanos , Recém-Nascido , Pneumopatias/diagnóstico , Microftalmia/diagnóstico , Linhagem , Gravidez , NatimortoRESUMO
Membrane skeleton protein 4.1 and other members of a family of proteins that link the cytoskeleton to the plasma membrane may play an integral role in cell communication during development. The polymerase chain reaction and degenerate oligodeoxynucleotide primers to consensus sequences in the putative membrane-binding domain of the protein 4.1 superfamily were used to isolate cDNAs encoding members of the zebrafish protein 4.1 family. Zebrafish stage- and tissue-specific first strand cDNA was used in the PCR. After the reaction, amplicons of the predicted size were sequenced to confirm their relationship to the protein 4.1 superfamily. One cDNA, with a high degree of similarity to a mouse novel band 4.1-like cDNA, was used to probe a zebrafish adult brain library. A 2.4-kb cDNA was isolated and found to encode a 619 amino acid polypeptide homologous to mouse novel band 4.1-like protein 4. Zebrafish nbl4 mRNA is maternally supplied and is expressed throughout embryogenesis. In adults, nbl4 is found in the ovary, eye, heart, and brain, but not in gut or skeletal muscle. When synthetic nbl4 mRNA is translated in vitro it binds calmodulin in a calcium-dependent manner. These data indicate that zebrafish nbl4 is a maternal transcript owing to its presence before the midblastula transition, and it is present later on in specific adult structures. The ability to bind calmodulin would suggest that the function of nbl4 protein may be potentially regulated via a calcium-calmodulin dependent mechanism.
Assuntos
Proteínas do Citoesqueleto , DNA Complementar/genética , Proteínas de Membrana/genética , Neuropeptídeos , Fatores de Transcrição , Proteínas de Peixe-Zebra , Peixe-Zebra/genética , Actinas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Fatores de Transcrição de Zíper de Leucina Básica , Cálcio/fisiologia , Calmodulina/metabolismo , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Dados de Sequência Molecular , Peso Molecular , Especificidade de Órgãos , RNA Mensageiro/análise , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Peixe-Zebra/embriologiaRESUMO
The mouse Otx2 gene is a homeobox transcription factor required as early as gastrulation for the proper development of the head. We compared gene expression profiles in wild-type and Otx2(-/-) 6.5 days postcoitum embryos by using a serial analysis of gene expression assay adapted to microdissected structures. Among a broader list, the study of six genes found to be differentially expressed allows defining a role for Otx2 in the orchestration of cell movements leading to the adequate organization of the embryo before gastrulation.
Assuntos
Gástrula/fisiologia , Perfilação da Expressão Gênica , Cabeça/embriologia , Proteínas de Homeodomínio/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Transativadores/fisiologia , Animais , Cistatina B , Cistatinas/genética , Citocinas , Ectoderma , Desenvolvimento Embrionário e Fetal , Endoderma , Etiquetas de Sequências Expressas , Feminino , Fatores de Crescimento de Fibroblastos/genética , Genótipo , Proteínas de Homeodomínio/genética , Humanos , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteína Nodal , Fatores de Transcrição Otx , Complexo Repressor Polycomb 2 , Proteínas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Transativadores/genética , Fatores de Transcrição , Fator de Crescimento Transformador beta/genética , Proteínas Wnt , Proteína Wnt4RESUMO
Dorsoventral patterning is regulated by a system of interacting secreted proteins involving BMP, Chordin, Xolloid and Twisted gastrulation (Tsg). We have analyzed the molecular mechanism by which Tsg regulates BMP signaling. Overexpression of Tsg mRNA in Xenopus embryos has ventralizing effects similar to Xolloid, a metalloprotease that cleaves Chordin. In embryos dorsalized by LiCl treatment, microinjection of Xolloid or Tsg mRNA restores the formation of trunk-tail structures, indicating an increase in BMP signaling. Microinjection of Tsg mRNA leads to the degradation of endogenous Chordin fragments generated by Xolloid. The ventralizing activities of Tsg require an endogenous Xolloid-like activity, as they can be blocked by a dominant-negative Xolloid mutant. A BMP-receptor binding assay revealed that Tsg has two distinct and sequential activities on BMP signaling. First, Tsg makes Chordin a better BMP antagonist by forming a ternary complex that prevents binding of BMP to its cognate receptor. Second, after cleavage of Chordin by Xolloid, Tsg competes the residual anti-BMP activity of Chordin fragments and facilitates their degradation. This molecular pathway, in which Xolloid switches the activity of Tsg from a BMP antagonist to a pro-BMP signal once all endogenous full-length Chordin is degraded, may help explain how sharp borders between embryonic territories are generated.