The zebrafish homologue of caldesmon is similar to the mammalian low molecular weight caldesmon (l-CaD). In this study, we explored the effects of caldesmon knockdown on vertebrate heart development in vivo. In a zebrafish model caldesmon was knocked down resulting in defective cardiac morphogenesis, muscularization and function. The data provide the first functional assessment of the role of caldesmon in cardiac development in vivo, and indicate that caldesmon is essential for proper cardiac organogenesis and function. Because caldesmon expression remarkably influences cardiac muscularization, the findings are relevant for designing future therapeutic strategies in the regeneration of cardiac damage. (C) 2008 Elsevier Inc. All rights reserved