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ZFIN ID: ZDB-PUB-140716-7
miR-19a replacement rescues cardiac and fin defects in zebrafish model of Holt-Oram Syndrome
Chiavacci, E., Cremisi, F., Guzzolino, E., Cellerino, A., Baumgart, M., D'aurizio, R., Pitto, L.
Date: 2014
Source: Cardiovascular research   103 Suppl 1: S99 (Abstract)
Registered Authors: Cellerino, Alessandro, Chiavacci, Elena
Keywords: none
MeSH Terms: none
PubMed: none Full text @ Cardiovasc. Res.
ABSTRACT
MicroRNAs (miRNAs) are short, single-stranded RNAs that anneal with complementary sequences in mRNAs thereby suppressing protein expression and often decreasing mRNA stability. Due to the high number of genes that are potentially targeted by one miRNA and to the relatively low number of different miRNAs coded in the genome, miRNAs are the best candidates to orchestrate gene expression in embryonic development and in response to inducing signals, by integrating distinct transcription factors pathways. Indeed, the manipulation of miRNA expression or function can have a profound impact on cellular phenotype. miRNA are critically involved in almost all the biological processes in health and disease including several cardiovascular disorders. Tbx5 is a transcription factor crucial for heart development and implicated in cardiac function. In human, TBX5 mutations are associated with Holt-Oram Syndrome (HOS), which is characterized by upper limb and congenital heart defects. In mouse model of HOS, expression profiling revealed that Tbx5 regulates hundreds of genes through complex transcriptional networks, acting both directly on gene expression and indirectly as "regulating of regulators". Our data indicate that miRNAs can be important effectors of Tbx5. The goal of our project is to better characterize the miRNAs/Tbx5 regulatory network with the aim: a) to understand the molecular roots of the complex HOS phenotype; b) to verify if it might be possible, by miRNA modulation, to restore the aberrant pathways generated by Tbx5 alteration.
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