2009

NEW INVESTIGATOR RECOGNITION

The Lymn Foundation made awards of $500 each to new investigators for presenting posters that contributed new insights and understanding of biological or disease processes in skeletal muscle during the recent conference on research developments in muscle biology:  “Making Muscle in the Embryo and Adult.”  Committees consisting of leaders at the conferences recommended the investigators.

2009 AWARD RECIPIENTS

Making Muscle in the Embryo and Adult

(http://www.ohri.ca/myogenesis/)

Itamar Harel

Distinct origins and genetic programs of head muscle satellite cells

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

Marie-Catherine Le Bihan

Are secreted microvesicles a novel mechanism of communication for skeletal muscle?

Institut de Myologie, Paris, France

2009 ABSTRACTS

Distinct origins and genetic programs of head muscle satellite cells

Itamar Harel, Elisha Nathan, Libbat Tirosh-Finkel, Hila Zigdon, Sylvia M. Evans, Eldad Tzahor

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel; University of California, San Diego, Skaggs School of Pharmacy La Jolla, CA

Recent studies have established that satellite cells in trunk and limb muscles derive from the somitic dermomyotome. In contrast, the embryonic origin(s) of satellite cells in the head musculature remain obscure. We used fate-mapping techniques in an avian model, as well as cre-lox genetic-based lineage analyses in mice, to show that satellite cells and their respective craniofacial muscles share a common embryonic origin. We further demonstrated that trunk (Pax3+) and cranial (Mesp1+) skeletal muscle cells and satellite cells derive from separate genetic lineages. Lineage tracing experiments with Isl1Cre mice demonstrated the robust contribution of Isl1+ splanchnic mesoderm cells to distinct jaw muscle-derived satellite cells, highlighting the heterogeneous nature of satellite cells in the head musculature. Transplantation of myofiber-associated Isl1 lineage-derived satellite cells into damaged limb muscle contributed to muscle regeneration. Consistent with the potent cardiogenic effect of Bmp signaling in embryonic head mesoderm, application of BMP4 induced cardiac gene expression (e.g., Isl1) in cranial- but not trunk derived satellite cells in culture. Finally, over expression of Isl1 in the branchiomeric muscles of chick embryos inhibited skeletal muscle differentiation in vitro and in vivo, suggesting that this gene plays a role in the quiescence and self-renewal of cardiovascular and skeletal muscle stem cell progenitors. 

Are secreted microvesicles a novel mechanism of communication for skeletal muscle?

Marie-Catherine Le Bihan, Anne Bigot, Søren S. Jensen, Jeanne Lainé, Adelina Rogowska-Wrzesinska, Gary R. Coulton, Vincent Mouly, Gillian S. Butler-Browne

Institut de Myologie, Paris, France; University of Southern Denmark, Odense, Denmark;  St. George’s, University of London, London, UK

Secreted signalling molecules play critical roles in regulating myogenesis during pre- and post-natal development. Growth factors and cytokines have been shown to regulate adult satellite cell myogenesis such as activation, proliferation and differentiation. Our main objective has been to characterize the secreted proteome or “secretome” of differentiating human myoblasts. By combining 3 powerful and complementary proteomic strategies, we have identified 965 non redundant secreted proteins. Using stringent computational analysis 257 proteins were classified as classical or leaderless secreted molecules, 85 of which were extracellular matrix components. Several known secreted proteins such as Galectin-1, IGF-II and Myostatin were also identified.  Among the “non secretory” proteins, computational analysis revealed that 434 had been found previously in microvesicles released from a broad range of cell types. The presence of these particles in both the culture supernatant and the muscle cells was confirmed by electron-microscopy. We extensively characterized the protein and mRNA cargo of those isolated microvesicles and have demonstrated that these secreted microvesicles can dock and fuse with differentiating muscle cells. We are thus able to postulate a novel mechanism of paracrine signaling for skeletal muscle cells which may play an important functional role in skeletal muscle homeostasis, regeneration and myogenesis.