{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMESP2 encodes a basic helix‐loop‐helix transcription factor that plays a central role in somitogenesis and vertebral segmentation. Early studies demonstrated that loss‐of-function mutations in MESP2 result in abnormal vertebral segmentation such as those observed in spondylocostal dysostosis, emphasizing its necessity for proper somite formation. In addition, detailed molecular dissection revealed that MESP2 contains a degradation domain and nuclear localization signals that regulate its transient expression and dosage, which in turn modulate the expression of downstream genes critical for somitogenesis and anterior–posterior patterning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations into MESP2 mutations uncovered its role in a specific subset of vertebral segmentation disorders. In patients presenting with spondylothoracic dysostosis (also known as Jarcho–Levin syndrome), researchers identified an E103X nonsense mutation—often in a founder effect setting in the Puerto Rican population—which, alone or in combination with other deleterious variants, disrupts MESP2 function and leads to a characteristic fusion of ribs along with extensive spine malformations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established function in skeletal patterning, MESP2 has also been implicated in early cardiac development. Expression studies have localized MESP2 in the developing outflow tract, where it regulates the transcriptional activities of key cardiac transcription factors. Functionally, variants in MESP2 were shown to perturb cell cycle regulators in cardiac neural crest cells, thereby inhibiting their proliferation and contributing to conotruncal heart defects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, while animal studies support a role for MESP2 in somitogenesis and associated disorders, mutation screening in a Chinese Han cohort of individuals with congenital scoliosis did not reveal any alterations in the MESP2 coding regions. This finding highlights that the contribution of MESP2 to the etiopathogenesis of vertebral malformations may be context‐ or population–dependent."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Neil V Whittock, Duncan B Sparrow, Merridee A Wouters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutated MESP2 causes spondylocostal dysostosis in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/421053"}], "href": "https://doi.org/10.1086/421053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15122512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15122512"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mitsuru Morimoto, Makoto Kiso, Nobuo Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2006.08.043"}], "href": "https://doi.org/10.1016/j.ydbio.2006.08.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16996494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16996494"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alberto S Cornier, Karen Staehling-Hampton, Kym M Delventhal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.04.014"}], "href": "https://doi.org/10.1016/j.ajhg.2008.04.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18485326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18485326"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Erge Zhang, Jianping Yang, Yang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MESP2 variants contribute to conotruncal heart defects by inhibiting cardiac neural crest cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Med (Berl) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00109-020-01929-4"}], "href": "https://doi.org/10.1007/s00109-020-01929-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32572506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32572506"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xu-sheng Qiu, Song Zhou, Hua Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation analysis of MESP2, HES7 and DUSP6 gene exons in patients with congenital scoliosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stud Health Technol Inform (2012)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22744456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22744456"}]}]}]}