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Unc(45b)-oordinated heart development

Cardiac development is a tightly regulated process that requires a network of specific cardiogenic transcription factors and the formation of functional sarcomeres to establish muscle contractility. Unc45b is a molecular chaperone that has been shown to be involved in the organisation of muscle sarcomeres during cardiac development, and this molecular chaperone is involved in the folding and activation of myosins in other eukaryotic cell types. Using mouse lines carrying Unc45b loss-of-function mutations, Henry Epstein and colleagues (p. 3893) now demonstrate that Unc45b regulates both sarcomere contractility and gene expression during cardiac development by interacting with myosins and the transcription factor GATA4, respectively. Unc45b is expressed in the heart of E9.5 mice, and Unc45b mutant mice display decreased cardiac contraction and fail to correctly develop the right hand side of the heart. Furthermore, loss of Unc45 leads to a reduction in sarcomeric myosin and GATA4 protein levels and decreased mRNA levels of GATA4 target genes. In addition, the authors illustrate that Unc45b can bind to both myosin and GATA4. They conclude that the chaperone helps to prevent the degradation of myosin and GATA4 and thereby contributes to the generation of cardiac contractility, as well as the specific activation of cardiac genes during development.