Project description:Aims: To examine the role of the basic Helix-loop-Helix (bHLH) transcription factor HAND1 in embryonic and adult myocardium. Methods and Results: Hand1 is expressed within the cardiomyocytes of the left ventricle (LV) and myocardial cuff between embryonic days (E) 9.5-13.5. Hand gene dosage plays an important role in ventricular morphology and the contribution of Hand1 to congenital heart defects requires further interrogation. Conditional ablation of Hand1 was carried out using either Nkx2.5 knockin Cre (Nkx2.5Cre) or a-myosin heavy chain Cre (aMhc-Cre) driver. Interrogation of transcriptome data via Ingenuity Pathway Analysis (IPA) reveals several gene regulatory pathways disrupted including translation and cardiac hypertrophy-related pathways. Embryo and adult hearts were subjected to histological, functional and molecular analyses. Myocardial deletion of Hand1 results in morphological defects that include cardiac conduction system defects, survivable interventricular septal defects (VSDs), and abnormal LV papillary muscles (PM). Resulting Hand1 conditional mutants are born at Mendelian frequencies; but the morphological alterations acquired during cardiac development result in, the mice developing diastolic heart failure. Conclusions: Collectively, these data reveal that Hand1 contributes to the morphogenic patterning and maturation of cardiomyocytes during embryogenesis and although survivable, indicate a role for Hand1 conduction system and papillary morphogenesis.
Project description:To investigate the signal communication from the endocardium to the trabecular myocardium, we performed single cell RNA sequencing (scRNA-seq) in E11.5 Hdac3 Tie2 knockout hearts and littermate control hearts
Project description:Adar1 is an essential gene for mouse embryonic development. Adar1 null mouse embryos dies around E11.5 because of massive apoptosis. Small RNA: 4 samples examined: wild type E11.0, ADAR1 null E11.0, wild type E11.5, ADAR1 null E11.5, mRNA-seq: wild type E11.5, ADAR1 null E11.5.
Project description:The development of vertebrate extremities is a complex process which requires a highly coordinated network of different transcriptional activities. The homeodomain transcription factor Shox2 is a key player in limb formation controlling neural, muscular and skeletal development. Here, we compared gene expression profiles of wildtype and Shox2 knockout limbs using microarray experiments to identify Shox2 target genes. Forelimbs of E11.5 mouse embryos were dissected and genotyped for RNA extraction. RNA from 3-4 embryos of 2 different pregnancies was used for hybridisation to 2 arrays per genotype (wildtype and Shox2 knockout) and compared.