Encyclopedia
mesoderm posterior bHLH transcription factor 2
- genes
1. Introdcution
Normal Function
The MESP2 gene provides instructions for making a transcription factor, which is a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The MESP2 protein controls the activity of genes in the Notch pathway, an important pathway in embryonic development. The Notch pathway plays a critical role in the development of the bones of the spine (vertebrae). Specifically, the MESP2 protein and the Notch pathway are involved in separating future vertebrae from one another during early development, in a complex process called somite segmentation. Although the exact mechanism of somite segmentation is unclear, it appears to require the activity of several proteins in the Notch pathway, including the NOTCH1 protein and the MESP2 protein, to be turned on and off (oscillate) in a specific pattern.
The MESP2 gene provides instructions for making a transcription factor, which is a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The MESP2 protein controls the activity of genes in the Notch pathway, an important pathway in embryonic development. The Notch pathway plays a critical role in the development of the bones of the spine (vertebrae). Specifically, the MESP2 protein and the Notch pathway are involved in separating future vertebrae from one another during early development, in a complex process called somite segmentation. Although the exact mechanism of somite segmentation is unclear, it appears to require the activity of several proteins in the Notch pathway, including the NOTCH1 protein and the MESP2 protein, to be turned on and off (oscillate) in a specific pattern.
The MESP2 protein regulates Notch activity by turning on (activating) genes in the Notch pathway, which ultimately block (repress) the activity of the NOTCH1 protein. Additionally, through unknown mechanisms, the MESP2 protein seems to mark the boundary separating future vertebrae from one another.
2. Health Conditions Related to Genetic Changes
2.1.
Spondylocostal dysostosis
MedlinePlus Genetics provides information about Spondylocostal dysostosis
More About This Health ConditionSpondylothoracic dysostosis
At least three mutations in the MESP2 gene have been found to cause spondylothoracic dysostosis, a condition characterized by abnormal development of bones in the spine and ribs. All of the known mutations replace one protein building block (amino acid) in the protein sequence. The most common mutation replaces the amino acid glutamate with a premature stop signal at position 103 (written as Glu103Ter or E103X). A similar mutation occurs at amino acid position 230 (written as Glu230Ter or E230X). The third mutation replaces the amino acid leucine with the amino acid valine at position 125 (written as Leu125Val or L125V). Most affected individuals have the Glu103Ter mutation in both copies of the MESP2 gene. However, a few people with spondylothoracic dysostosis have the Glu103Ter mutation in one copy of the MESP2 gene and either the Leu125Val or the Glu230Ter mutation in the other copy.
At least three mutations in the MESP2 gene have been found to cause spondylothoracic dysostosis, a condition characterized by abnormal development of bones in the spine and ribs. All of the known mutations replace one protein building block (amino acid) in the protein sequence. The most common mutation replaces the amino acid glutamate with a premature stop signal at position 103 (written as Glu103Ter or E103X). A similar mutation occurs at amino acid position 230 (written as Glu230Ter or E230X). The third mutation replaces the amino acid leucine with the amino acid valine at position 125 (written as Leu125Val or L125V). Most affected individuals have the Glu103Ter mutation in both copies of the MESP2 gene. However, a few people with spondylothoracic dysostosis have the Glu103Ter mutation in one copy of the MESP2 gene and either the Leu125Val or the Glu230Ter mutation in the other copy.
Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, the NOTCH1 protein is abnormally active and the boundary separating future vertebrae from one another does not form. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis.
Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, the NOTCH1 protein is abnormally active and the boundary separating future vertebrae from one another does not form. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis.
More About This Health Condition3. Other Names for This Gene
- bHLHc6
- class C basic helix-loop-helix protein 6
- mesoderm posterior 2 homolog (mouse)
- mesoderm posterior basic helix-loop-helix transcription factor 2
- mesoderm posterior protein 2
- MESP2_HUMAN
- SCDO2
References
- Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N,Ellard S, Young E, Ramirez N, Carlo SE, Torres J, Emans JB, Turnpenny PD,Pourquié O. Mutations in the MESP2 gene cause spondylothoracicdysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008 Jun;82(6):1334-41. doi:10.1016/j.ajhg.2008.04.014.
- Ferjentsik Z, Hayashi S, Dale JK, Bessho Y, Herreman A, De Strooper B, delMonte G, de la Pompa JL, Maroto M. Notch is a critical component of the mousesomitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009 Sep;5(9):e1000662. doi: 10.1371/journal.pgen.1000662.
- Gibb S, Maroto M, Dale JK. The segmentation clock mechanism moves up a notch. Trends Cell Biol. 2010 Oct;20(10):593-600. doi: 10.1016/j.tcb.2010.07.001.
- Morimoto M, Takahashi Y, Endo M, Saga Y. The Mesp2 transcription factorestablishes segmental borders by suppressing Notch activity. Nature. 2005 May19;435(7040):354-9.
- Oginuma M, Takahashi Y, Kitajima S, Kiso M, Kanno J, Kimura A, Saga Y. Theoscillation of Notch activation, but not its boundary, is required for somiteborder formation and rostral-caudal patterning within a somite. Development. 2010May;137(9):1515-22. doi: 10.1242/dev.044545.
- Sasaki N, Kiso M, Kitagawa M, Saga Y. The repression of Notch signaling occursvia the destabilization of mastermind-like 1 by Mesp2 and is essential forsomitogenesis. Development. 2011 Jan;138(1):55-64. doi: 10.1242/dev.055533.
- Sparrow DB, Chapman G, Turnpenny PD, Dunwoodie SL. Disruption of the somiticmolecular clock causes abnormal vertebral segmentation. Birth Defects Res CEmbryo Today. 2007 Jun;81(2):93-110. Review.
- Turnpenny PD, Sloman M, Dunwoodie S; ICVS (International Consortium forVertebral Anomalies and Scoliosis). Spondylocostal Dysostosis, AutosomalRecessive. 2009 Aug 25 [updated 2017 Dec 21]. In: Adam MP, Ardinger HH, Pagon RA,Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet].Seattle (WA): University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK8828/
- Whittock NV, Sparrow DB, Wouters MA, Sillence D, Ellard S, Dunwoodie SL,Turnpenny PD. Mutated MESP2 causes spondylocostal dysostosis in humans. Am J Hum Genet. 2004 Jun;74(6):1249-54.
