RESUMO
Bone morphogenetic protein 4 (Bmp4), a vertebrate homolog of Drosophila decapentaplegic (dpp), encodes a signaling protein with multiple functions during embryogenesis. Most mouse embryos homozygous for the Bmp4(tm1blh) null allele die around the time of gastrulation, with little or no mesoderm. Two independently derived Bmp4(tm1) mutations were backcrossed onto the C57BL/6 genetic background. Several independently expressed, incompletely penetrant abnormalities were observed in heterozygotes, including cystic kidney, craniofacial malformations, microphthalmia, and preaxial polydactyly of the right hindlimb. In addition, heterozygotes were consistently underrepresented at weaning. These results indicate that Bmp4 gene dosage is essential for the normal development of a variety of organs and for neonatal viability. Two mutations that enhance the penetrance and expressivity of the polydactylous phenotype were identified: Gli3(XtJ), a deletion mutation involving a gene encoding a zinc-finger protein related to Drosophila cubitus interruptus, and Alx4(tm1rwm), a targeted null mutation in a gene encoding a paired class homeoprotein related to Drosophila aristaless. All double Bmp4(tm1); Gli3(XtJ) heterozygotes have extensive anterior digit abnormalities of both fore- and hindlimbs, while all double Bmp4(tm1); Alx4(tm1) heterozygotes display ectopic anterior digits only on the hindlimbs. These genetic interactions suggest a model for the multigenic control of anterior digit patterning during vertebrate limb development.
Assuntos
Proteínas Morfogenéticas Ósseas/deficiência , Proteínas Morfogenéticas Ósseas/genética , Anormalidades Congênitas/genética , Proteínas de Ligação a DNA/genética , Proteínas do Tecido Nervoso , Proteínas Repressoras , Proteínas de Xenopus , Animais , Proteína Morfogenética Óssea 4 , Osso e Ossos/patologia , Cruzamentos Genéticos , Proteínas de Ligação a DNA/biossíntese , Desenvolvimento Embrionário e Fetal/genética , Feminino , Morte Fetal , Gástrula , Genótipo , Heterozigoto , Rim/embriologia , Rim/patologia , Fatores de Transcrição Kruppel-Like , Masculino , Mesoderma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Mutagênese , Osteogênese , Fenótipo , Polidactilia/genética , Caracteres Sexuais , Fatores de Transcrição/genética , Proteína Gli3 com Dedos de ZincoRESUMO
Pax6 expression in the diencephalon of the mouse embryo is restricted both antero-posteriorly and dorso-ventrally, with changes in level occurring at prosomere boundaries. Small eye (Pax6Sey-1Neu) mice homozygous for Pax6 mutations have multiple defects in early forebrain development. In the diencephalon of Pax6Sey-1Neu/Pax6Sey-1Neu mice there is an apparent enlargement of the zona limitans (the boundary region between prosomeres p2 and p3), and a blurring of the p1-p2 boundary. PAX6 function is also required for the normal development of the posterior commissure at the midbrain-p1 boundary. In the posterior diencephalon PAX6 appears to regulate its own transcription, and that of Wnt7b. In p2 and p3, ventral markers are expressed more dorsally than normal, and this is accompanied in p3 by a reduction in the size of the zona incerta. Thus, PAX6 is essential for the normal development and regionalization of the diencephalon.
