Current Environment:

Muscular Disorders | Overview


The Zon lab, in collaboration with Wagers lab, has used a cross species in vivo screening approach to assess the engraftment efficiency of muscle progenitor cells in transplanted recipients. Transplantation of exogenous muscle progenitor cells has been considered as an approach to enhance muscle function and repair, particularly in genetic muscle diseases like Duchenne Muscular Dystrophy, but the application of this approach has been limited due to the typically poor engraftment efficiency of cultured progenitors. Thus, to overcome this hurdle and reveal determinants of efficient progenitor cell engraftment in muscle, Zon lab developed a novel screening platform employing both zebrafish and mice. Then, applied this system to discover chemical compounds that promote muscle progenitor engraftment in vivo.

Muscle cells derived from zebrafish blastomeres and treated ex-vivo with candidate biomolecules are transplanted into the flanks of immune-suppressed adult zebrafish. Using highly sensitive limit-dilution assays, potential “hits” from our primary screen were identified and re-evaluated in replicate transplantation experiments. Using a bioluminescence imaging, Zon lab further ascertained if the “hits” enhance satellite cell engraftment in mice as well, indicating conservation of the engraftment-promoting activities of these compounds across vertebrate species. Furthermore, studies in mutant fish transplanted with pre-transplantation treated cells showed higher engraftment efficiency, significantly better swimming performance and an improved ability to sustain position against a water current. The success of this cross-species approach in uncovering evolutionary conserved pathways regulating muscle regeneration defines a new paradigm for the discovery of pro-myogenic drugs and pathways and suggests new potential opportunities for treating muscle disease by enhancing the therapeutic contributions of transplanted muscle progenitors.