Alberto Stolfi: "Combinatorial transcription factor logic regulates muscle subtype-specific multinucleation in a non-vertebrate chordate"

Vertebrate myoblast fusion allows for multinucleated muscle fibers to compound the size and strength of individual mononucleated cells, but the evolution of this important process is poorly understood. The phylum Chordata hosts closely related groups that span distinct myoblast fusion states: no fusion in cephalochordates, facultative fusion and multinucleation in tunicates, and extensive, obligatory fusion in vertebrates. To elucidate how these differences may have evolved, we studied the evolutionary origins and function of membrane-coalescing agents Myomaker and Myomixer in various groups of chordates. We found that Myomaker likely arose through gene duplication in the last common ancestor of tunicates and vertebrates, while Myomixer appears to have evolved de novo only after vertebrates diverged from tunicates. We also found that, in the tunicate Ciona, facultative activation of Myomaker in multinucleated juvenile siphon and body wall muscles (but not mononucleated larval tail muscles) is carried out by a post-metamorphic myogenesis program based on the cooperative activity of the transcription factors MRF (MyoD) and Ebf (COE). Our findings suggest an evolutionary model of chordate-specific fusogens and illustrate how new genes and their cell type-specific expression patterns can shape the emergence of novel morphogenetic traits and mechanisms.

Alberto Stolfi obtained his PhD in Molecular and Cell Biology from UC Berkeley under the supervision of Mike Levine, and did postdoctoral work at New York University with Lionel Christiaen. In 2017 he started as an Assistant Professor in the School of Biological Sciences at the Georgia Institute of Technology.