Bhylahalli Purushottam Srinivas, Jennifer Woo, Wan Ying Leong and Sudipto Roy.
Skeletal muscles arise by fusion of precursor cells, myoblasts, into multinucleate fibers. In vertebrates, mechanisms controlling this essential step in myogenesis remain poorly understood. Here we provide evidence that Kirrel, a homolog of receptor proteins that organize myoblast fusion in Drosophila melanogaster, is necessary for muscle precursor fusion in zebrafish. Within the developing somites, Kirrel expression localized to membranes of fusion-competent myoblasts of the fast-twitch lineage. Unlike wild-type myoblasts that form spatially arrayed syncytial (multinucleated) fast myofibers, those deficient in Kirrel showed a significant reduction in fusion capacity. Inhibition of Rac, a GTPase and most downstream intracellular transducer of the fusion signal in D. melanogaster, also compromised fast muscle precursor fusion in zebrafish. However, unlike in D. melanogaster, constitutive Rac activation in zebrafish led to hyperfused giant syncytia, underscoring an entirely new function of the protein in zebrafish for gating the number and polarity of fusion events. These findings uncover a substantial degree of evolutionary conservation in the genetic regulation of myoblast fusion.
Published in Nature Genetics , 39 (6): pg781 - pg786, 2007.
Accompanying “News and Views” in Nature Genetics, 39 (6): pg704 - pg705, 2007.
Awarded the Genetics Society of America prize for best poster at the 7th International Conference on Zebrafish Development and Genetics, Madison, USA, 2006.