| The vertebrate axial musculoskeletal system arises from somites---segmentally arranged blocks of mesoderm that prefigure the metamerism of the spinal column. The axial musculature and skeleton are known to originate from two distinct somitic compartments, the myotome and sclerotome. This dissertation describes the developmental origin and regulation of the axial tendons, which mediate attachment between the epaxial muscles and vertebrae, and the intercostal muscles and ribs. Through analysis of the expression of Scleraxis ( Scx), a basic helix-loop-helix transcription factor expressed in the mature tendons of the limb and trunk as well as in their progenitor populations, we identify a previously undetected somitic compartment of Scx-expressing axial tendon progenitors, here termed the syndetome. We identify the lateral edge of the sclerotome as the origin of the syndetome, and demonstrate how crucial interactions between the somitic muscle and cartilage cell lineages lead to specification of the tendon lineage.;This dissertation also addresses the molecular mechanisms of syndetome formation, showing that the fourth compartment is generated when Fibroblast growth factors (Fgfs) secreted from the myotome's center induce the anterior and posterior sclerotome abutting the myotome to adopt a tendon cell fate. Through a combination of gain-of-function and loss-of-function experiments, we demonstrate that this myotomal Fgf signaling pathway is both necessary and sufficient for induction of Scx expression in chick and mouse during somite development. Additionally, we provide evidence that the Fgf signal responsible for inducing the Scx expression domain is directly received by the anterior and posterior sclerotome, that the Fgf8 synexpression group members Pea3 and Erm are coexpressed with Scx, and that the activity of Pea3 and Erm is necessary and sufficient for Fgf-dependent induction of Scx.;Finally, this study reveals that the cartilage and tendon lineages of the sclerotome are alternate, mutually exclusive fate choices. We show that the signals promoting the sclerotome to adopt the tendon fate inhibit the cartilage fate, and vice versa, and that cartilage differentiation is required to actively repress tendon development in the lateral sclerotome. Thus, a crucial and fine-tuned balance must be negotiated between these two lineages in order for proper development and assembly of the axial musculoskeletal system to proceed. |
