Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development

Abstract

Proper formation of the musculoskeletal system requires the coordinated development of the muscle, cartilage and tendon lineages arising from the somitic mesoderm. During early somite development, muscle and cartilage emerge from two distinct compartments, the myotome and sclerotome, in response to signals secreted from surrounding tissues. As the somite matures, the tendon lineage is established within the dorsolateral sclerotome, adjacent to and beneath the myotome. We examine interactions between the three lineages by observing tendon development in mouse mutants with genetically disrupted muscle or cartilage development. Through analysis of embryos carrying null mutations in Myf5 and Myod1, hence lacking both muscle progenitors and differentiated muscle, we identify an essential role for the specified myotome in axial tendon development, and suggest that absence of tendon formation in Myf5/Myod1 mutants results from loss of the myotomal FGF proteins, which depend upon Myf5 and Myod1 for their expression, and are required, in turn, for induction of the tendon progenitor markers. Our analysis of Sox5/Sox6 double mutants, in which the chondroprogenitors are unable to differentiate into cartilage,reveals that the two cell fates arising from the sclerotome, axial tendon and cartilage are alternative lineages, and that cartilage differentiation is required to actively repress tendon development in the dorsolateral sclerotome.

Characterization of the DNA-binding Properties of the Mohawk Homeobox Transcription Factor

“…Sox6 has been shown to be an important regulator during musculoskeletal development and fiber type specification (35)(36)(37)43). Sox6 possesses a redundant function with Sox5 during the differentiation of chondrocytes (44) and is required to block cells of the sclerotome from entering the tendon lineage (45). In skeletal muscle, Sox6 suppresses slow twitch fiber development through the direct repression of Myh7 transcription (34,35).…”

In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review

“…Tendon differentiation is mediated through the Smad signalling pathway of TGFβ (Lorda-Diez et al, 2009;Pryce et al, 2009). Disruption of FGF and TGFβ signalling leads to expression inhibition of the tendon associated transcription factor scleraxis (Scx) (Brent and Tabin, 2004;Brent et al, 2005;EdomVovard et al, 2002;Pryce et al, 2009). Scx is a basic helix-loop-helix transcription factor, involved in regulating expression of other tenogenic markers such as tenascin-C, tenomodulin, Mohawk and type I collagen.…”

A MINI REVIEW ON THE BASIC KNOWLEDGE ON TENDON: REVISITING THE NORMAL & INJURED TENDON

“…The FGF transcription effectors (Pea3 and Erm) are necessary for TP marker Scx expression in the somite to be expressed (29,30 …”

“…This causes the Sox9-expressing mesenchymal condensations to begin expressing tendon markers. It worth noting that when the differentiation of one cell fate is blocked, the other is adopted (30).…”