RESUMO
Transcription factor Gata3 is implicated in the formation of autosomal dominant hypoparathyroidism, sensorineural deafness, and renal anomaly (HDR) syndrome. We pursued to identify the potential Gata3 target genes by profiling the gene expression pattern in E9.5 Gata3-/- mouse embryos. Altogether four independent microarray hybridizations were carried out on NIA Mouse15K cDNA arrays. We discovered two hundred and sixty one genes that are downregulated in Gata3 mutant embryos at E9.5 (with a minimal 2.0-fold change). The majority of the differentially expressed genes belong to two functional groups--genes involved in transcription regulation and cellular signaling. One of the genes discovered to be downregulated in Gata3 mutant embryos was tumor suppressor gene Disabled 2. The validity of this finding was checked by using the whole mount in situ hybridization technology. This study revealed that the sites, where Dab2 is downregulated in the mutant embryos partly overlap with the Gata3 expression domains, including the mid-embryo region, branchial arches and facio-acoustic (VII-VIII) neural crest complex. This is the first time when tumor supressor gene Dab2 is shown to be implicated in the defective phenotype of Gata3 mutant mice.
Assuntos
Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Transativadores/genética , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Proteínas Reguladoras de Apoptose , Região Branquial/embriologia , Fator de Transcrição GATA3 , Perfilação da Expressão Gênica , Perda Auditiva Neurossensorial/congênito , Hipoparatireoidismo/congênito , Nefropatias/congênito , Camundongos , Camundongos Knockout , Crista Neural/embriologia , Análise de Sequência com Séries de OligonucleotídeosRESUMO
The ultrastructural localization of adenylate cyclase (E.C. 4.6.1.1.) and cAMP phosphodiesterase (PDE) (E.C. 3.1.4.17.) in the ectoderm of the developmental stage 4 chick embryo was studied. Adenylate cyclase was localized in the lateral surfaces of the ectodermal cells. In the primitive streak cells the enzymatic activity was observed on all the lateral surfaces, whereas in the periphery of the blastoderm the reaction product was localized in the apical parts of the lateral plasma membranes only.cAMP PDE localized in the apical cytoplasm of the ectodermal cells, with highest activity in the globular projections.
