WNT signaling in mammalian myogenesis

Vertebrate skeletal muscle originates from somites, segmented mesodermal tissue that develop on both sides of the embryonic axis (figure1). Muscles of the deep back arise from the medial somite, whereas muscles of the limb and body wall arise from the lateral somite. Myf5 (figure 2) and MyoD (figure 3) are essential genes that confer commitment to the medial and lateral fates, respectively. Mice that lack Myf5 and MyoD do not develop these precursor myoblast pools, and consequently do not form skeletal muscles. Because these two genes dictate where and what types of muscles will form, the precise spatial and temporal regulation of Myf5 and MyoD is crucial to the proper formation of the entire musculature.

Myogenesis is dependent upon signals derived from tissues adjacent to the somite, including the neural tube (NT), notochord (NC), and surface ectoderm (SE). Co-culture experiments have demonstrated that members of the WNT family, expressed in the neural tube and surface ectoderm, provide the inductive cues for Myf5 and MyoD expression. However, the mechanism by which WNT does so remains unknown. My objective is to investigate the molecular pathways by which WNTs regulate Myf5 and MyoD.