SRA

Purpose: The aim of the study was to decipher the function of Creld1 in the myocardium during embryonic and postnatal heart development. Methods: We generated conditional knockout (KO) mice lacking Creld1 in cells expressing the Myosine Heavy Chain (MyHC, myocardial cells). Embryonic (E13.5, n=4) and postnatal (P3, n=3) hearts from both wild-type (WT) and KO mice were isolated and postnatal hearts were further split into atria and ventricles. Total RNA was extracted, mRNA purified, converted into cDNA and sequenced using a NextSeq500 system (Illumina).The reads passing default quality filters were aligned to the mouse genome (mm10). Results: More than 5.1 million aligned reads were retrieved in each sample.The expression profiles of the postnatal KO samples underline drastic anormalies in the hearts and commencing heart failure particularly in the atria. In embryonic KO hearts the transciption of Notch1 signalling components and consequently extracellular matrix (ECM) homeostasis was altered, whereas transcription in Nfatc1 and Vegf signalling pathways was unchanged. Conclusion: This study shows that myocardial Creld1 is a key morphogenic factor in the developing heart and as it regulates Notch1 signalling and, thereby, the ECM during cardiac wall development. Overall design: Transcriptomes of myocardium-specific Creld1 knockout mice were compared to wild-type controls at E13.5 and P3.