The Basic Biology of Aging at the University of Washington
Yablonka-Reuveni Zipora, Ph.D.

Biosketch Information
Email: reuveni@u.washington.edu

The goal of my research is to gain insight into the regulation of the myogenic precursors (satellite cells) in postnatal and adult skeletal muscle. These precursor cells are situated underneath the basement membrane of the myofibers. In young animals at least some of the satellite cells are proliferative, adding myonuclei to the enlarging muscle fibers. In the adult muscle the satellite cells are mitotically quiescent, but can be recruited into proliferation following various muscular stresses ranging from a major trauma to exercise and hypertrophy.

The mechanisms controlling the quiescent/proliferative/differentiative states of the satellite cells are not yet resolved. The status of the satellite cells in the aging muscle is poorly understood as well.

Our recent studies have focused on the role of the fibroblast growth factors and their receptors during myogenesis of satellite cells. Our investigations have led us to propose that one of the members of the FGF family (i.e., FGF6) and one of the transmembrane FGF receptors (i.e., FGFR4) might play a critical role during postnatal myogenesis. Our hypothesis is that interplay between FGFR4 and the myogenic regulatory transcription factor MyoD regulates the 'fine tuning' of the transition from proliferation to differentiation. To test the importance of these different regulatory factors we are analyzing myogenesis in mutant mice lacking various FGFs-FGFRs and in mice lacking myogenic specific transcription factors. Many of the studies are performed with isolated myofibers and with tissue-dissociated myoblasts.

Satellite cells have been thought to be the sole source of myogenic precursors in the postnatal muscle. However, recent studies by various laboratories have suggested that other cell types might also be capable of contributing skeletal muscle precursors in the adult. In recent years we have been analyzing the possible contribution of skeletal muscle precursors by vascular smooth muscle cells. This 'unorthodox' path of myogenesis might be used following skeletal muscle injury when a large supply of myoblasts is necessary for tissue repair. The skeletal muscle tissue is enriched in blood vessels and capillaries which are also damaged and subsequently being repaired following trauma to skeletal muscle. We also study the possibility that the satellite cells represent a pool of cells that rapidly supply differentiated progeny for immediate muscle repair while other cells in the skeletal muscle are the actual skeletal muscle stem cells capable of self-renewal along with the production of satellite cells.

Selected Relevant Publications
Yablonka-Reuveni, Z., Seger, R., and Rivera, A.J. (1999). Fibroblast growth factor promotes recruitment of skeletal muscle satellite cells in young and old rats. J. Histochem. Cytochem. 47: 23-42.

Yablonka-Reuveni, Z., Rudnicki, M. A., Rivera, A.J., Primig, M., Anderson, J.E., and P. Natanson. (1999). The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD. Dev. Biol. 210: 440-455.

Kästner, S., Elias, M.C., Rivera, A.J., Yablonka-Reuveni, Z. (2000). Gene expression patterns of the fibroblast growth factors and their receptors during myogenesis of rat satellite cells. J.Histochem. Cytochem 48:1079-1096.

Graves, D.C., and Z. Yablonka-Reuveni. (2000) Vascular smooth muscle cells spontaneously adopt a skeletal muscle phenotype: a unique Myf5-/MyoD+ program J. Histochem. Cytochem. 48: 1173-1194.

Yablonka-Reuveni, Z., and B.M. Paterson (2001) MyoD and myogenin expression patterns in cultures of fetal and adult chicken myoblasts. J. Histochem. Cytochem. 49: 455-462.