The neuronal co-repressor CoREST: An additional marker for immature neurons within the olfactory epithelium of the developing and adult mouse

Heart failure due to the loss of functional cardiomyocytes is one of the most frequent cardiovascular diseases. Understanding the genetic network that leads to functional cardiomyocytes is the first step to develop future therapies. Two murine engineerd mesodermal ESC lines as well as a cardiac-specific ESC line were established in our group. A global transcriptome analysis yielded two genes up-regulated in cardiomyocytes, two genes up-regulated in cardiomyocytes and pure mesodermal cells and two genes up-regulated in pure mesodermal, but down-regulated in cardiomyocytes (Doss et al., 2007a+b*). We were interested in a fast screen for the functional role of transcripts with unknown function (TUFs) for an intact activity of the heart. Therefore we searched for homologues in the zebrafish genome and performed a morpholino-based knockdown approach. Morpholino-oligonucleotide injections caused highly specific cardiovascular defects in the majority of them such as altering of heart morphology and defects to a different extent and penetrance. For knockdown of the gene expression in murine ESCs to further analyze the potential for cellular differentiation, short hairpin RNA (shRNA) was used. PCR, Immunohistochemistry and microarray analysis indicated that the knockdown suppresses the expression of specific mesodermal and cardiac marker genes significantly. The present results demonstrate that, the in cardiomyocytes specifically up-regulated, genes play a crucial role in cardiomyogenesis.