RESUMEN
The Drosophila genes eyeless, eyes absent, sine oculis and dachshund cooperate as components of a network to control retinal determination. Vertebrate homologues of these genes have been identified and implicated in the control of cell fate. We present the cloning and characterization of mouse Dach2, a homologue of dachshund. In situ hybridization studies demonstrate Dach2 expression in embryonic nervous tissues, sensory organs and limbs. This pattern is similar to mouse Dach1, suggesting a partially redundant role for these genes during development. In addition, we determine that Dach2 expression in the forebrain of Pax6 mutants and dermamyotome of Pax3 mutants is not detectably altered. Finally, genetic mapping experiments place mouse Dach2 on the X chromosome between Xist and Esx1. The identification of human DACH2 sequences at Xq21 suggests a possible role for this gene in Allan-Herndon syndrome, Miles-Carpenter syndrome, X-linked cleft palate and/or Megalocornea.
Asunto(s)
Proteínas de Drosophila , Proteínas Nucleares/química , Proteínas Nucleares/genética , Secuencia de Aminoácidos , Animales , Northern Blotting , Mapeo Cromosómico , Clonación Molecular , ADN Complementario/metabolismo , Proteínas de Unión al ADN/biosíntesis , Drosophila , Proteínas del Ojo , Genotipo , Proteínas de Homeodominio/biosíntesis , Humanos , Hibridación in Situ , Ratones , Ratones Endogámicos C57BL , Modelos Genéticos , Datos de Secuencia Molecular , Sistema Nervioso/embriología , Proteínas Nucleares/biosíntesis , Factor de Transcripción PAX3 , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box , Estructura Terciaria de Proteína , Proteínas Proto-Oncogénicas/biosíntesis , ARN/metabolismo , ARN Largo no Codificante , ARN no Traducido/biosíntesis , Proteínas Represoras , Homología de Secuencia de Aminoácido , Factores de Tiempo , Distribución Tisular , Factores de Transcripción/biosíntesis , Cromosoma XRESUMEN
Drosophila dachshund is necessary and sufficient for compound eye development and is required for normal leg and brain development. A mouse homologue of dachshund, Dach1, is expressed in the developing retina and limbs, suggesting functional conservation of this gene. We have generated a loss-of-function mutation in Dach1 that results in the abrogation of the wild-type RNA and protein expression pattern in embryos. Homozygous mutants survive to birth but exhibit postnatal lethality associated with a failure to suckle, cyanosis, and respiratory distress. The heart, lungs, kidneys, liver, and skeleton were examined to identify factors involved in postnatal lethality, but these organs appeared to be normal. In addition, blood chemistry tests failed to reveal differences that might explain the lethal phenotype. Gross examination and histological analyses of newborn eyes, limbs, and brains revealed no detectable abnormalities. Since Dach1 mutants die shortly after birth, it remains possible that Dach1 is required for postnatal development of these structures. Alternatively, an additional Dach homologue may functionally compensate for Dach1 loss of function.
