Scleraxis

Work done by Cserjesi and colleagues; suggest scleraxis as a novel genetic marker specific for connective tissues such as tendons and ligaments. It is thought that early scleraxis expressing progenitor cells lead to the eventual formation of tendon tissue and other muscle attachments (Cserjesi et al., 1995). Scleraxis is involved in mesoderm formation and is expressed in the syndetomal compartment of developing somites (Brent et al., 2003). Scleraxis is a member of the basic helix - loop - helix (bHLH) superfamily of transcription factors. As reviewed by Kadesch in 1993, bHLH transcription factors have been shown to have a wide array of functions, in developmental processes. More precisely, they have critical roles in the control of cellular differentiation, proliferation and regulation of oncogenesis (Kadesch 1993; Olson and Klein 1994; Jan and Jan 1993). To date, 242 eukaryotic proteins belonging to the HLH superfamily have been reported. They have varied expression patterns in all eukaryotes from yeast to humans (Atchley et al., 1997).

Structurally, bHLH proteins are characterised by a “highly conserved domain containing a stretch of basic amino acids adjacent to two amphipathic α-helices separated by a loop” (Wilson-Rawls et al., 2004; reviewed in Ellenberger et al., 1994). These helices have important functional properties, forming part of the DNA binding and transcription activating domains. With respect to scleraxis, the bHLH region spans amino acid residues 78 to 131. A proline rich region is also predicted to lie between residues 161-170. A stretch of basic residues, which aids in DNA binding, is found closer to the N terminal end of scleraxis (Wolf et al., 1991; Cserjesi et al., 1995) (figure 4). Interestingly, HLH proteins that lack this basic domain have been shown to negatively regulate the activities of bHLH proteins and are called inhibitors of differentiation (Id) (Benezra et al., 1990). Basic HLH proteins function normally as dimers and bind to a specific hexanucleotide DNA sequence (CAANTG) known as an E Box thus switching on the expression of various genes involved in cellular development and survival (Ephrussi et al., 1985). Zoher Kapacee