| scleraxis homolog A (mouse) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | SCXA | ||||||
| NCBI gene | 333927 | ||||||
| HGNC | 24312 | ||||||
| OMIM | 609067 | ||||||
| UniProt | Q7RTU7 | ||||||
| Other data | |||||||
| Locus | Chr. 8q24.3 | ||||||
| |||||||
| scleraxis homolog B (mouse) | |
|---|---|
| Identifiers | |
| Symbol | SCXB |
| NCBI gene | 642658 |
| HGNC | 32322 |
| RefSeq | XM_926116 |
| Other data | |
| Locus | Chr. 8q24.3 |
Thescleraxisprotein is a member of thebasic helix-loop-helix (bHLH) superfamily oftranscription factors.[1] Currently two genes (SCXA andSCXB respectively) have been identified to code for identical scleraxis proteins.
It is thought that early scleraxis-expressingprogenitor cells lead to the eventual formation oftendon tissue and other muscle attachments.[1] Scleraxis is involved inmesoderm formation and is expressed in the syndetome (a collection of embryonic tissue that develops into tendon and blood vessels) of developingsomites (primitive segments or compartments of embryos).[2]
The syndetome location within the somite is determined byFGF secreted from the center of the myotome (a collection of embryonic tissue that develops intoskeletal muscle)- the FGF then induces the adjacentanterior andposterior sclerotome (a collection of embryonic tissue that develops into theaxial skeleton) to adopt a tendon cell fate. This ultimately places future scleraxis-expressing cells between the two tissue types they will ultimately join.[3]
Scleraxis expression will be seen throughout the entire sclerotome (rather than just the sclerotome directly anterior and posterior to the myotome) with an overexpression ofFGF8, demonstrating that all sclerotome cells are capable of expressing scleraxis in response to FGF signaling. While the FGF interaction has been shown to be necessary for scleraxis expression, it is still unclear as to whether the FGF signaling pathway directly induces the syndetome to secrete scleraxis, or indirectly through a secondary signaling pathway. Most likely, the syndetomal cells, through careful reading of the FGFconcentration (coming from the myotome), can precisely determine their location and begin expressing scleraxis.[3] Much of embryonic development follows this model of inducing specific cell fates through the reading of surrounding signaling molecule concentration gradients.
bHLH transcription factors have been shown to have a wide array of functions indevelopmental processes.[4] More precisely, they have critical roles in the control ofcellular differentiation,proliferation and regulation ofoncogenesis.[4][5][6] To date, 242eukaryotic proteins belonging to the HLH superfamily have been reported. They have varied expression patterns in all eukaryotes from yeast to humans.[7]
Structurally, bHLH proteins are characterised by a “highly conserved domain containing a stretch of basicamino acids adjacent to twoamphipathicα-helices separated by a loop”.[8][9]
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.[1][10]
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).[11] Basic HLH proteins function normally as dimers and bind to a specific hexanucleotide DNA sequence (CAANTG) known as anE-box thus switching on the expression of various genes involved in cellular development and survival.