This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2.[6] Msx2 is a homeobox gene localized on human chromosome 5 that encodes a transcription repressor and activator (MSX-2) responsible for craniofacial and limb-bud development. Cells will express msx2 when exposed to signaling molecules BMP-2 and BMP-4 in situ.[7] Expression of msx2 leads to the proliferation, migration and osteogenic differentiation of neural crest cells during embryogenesis and bone fracture.[8] It is well documented that expression of cell-cell adhesion molecules such as E-cadherins will promote structural integrity and an epithelial arrangement of cells, while expression of N-cadherin and vimentin promote mesenchymal arrangement and cell migration.[9][10] Msx2 downregulates E-cadherins and upregulates N-cadherin and vimentin which indicates its role in inducing epithelial mesenchymal transition (EMT). Germline knockout mice have been created for this gene (Msx2 +/-) in order to examine functional loss.[11] Clinical studies on craniosynostosis, or the premature fusion of cranial structures, have shown the condition to be genetically linked to mutation in the msx2 homeobox gene.[12]
^ abcGRCh38: Ensembl release 89: ENSG00000120149 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Takahashi C, Akiyama N, Matsuzaki T, Takai S, Kitayama H, Noda M (May 1996). "Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene". Oncogene. 12 (10): 2137–46. PMID 8668339.
^Kostrzewa M, Grady DL, Moyzis RK, Flöter L, Müller U (March 1996). "Integration of four genes, a pseudogene, thirty-one STSs, and a highly polymorphic STRP into the 7-10 Mb YAC contig of 5q34-q35". Human Genetics. 97 (3): 399–403. doi:10.1007/BF02185781. PMID 8786091. S2CID 12647370.
^Rifas L (July 1997). "Gestational exposure to ethanol suppresses msx2 expression in developing mouse embryos". Proc Natl Acad Sci U S A. 94 (14): 7549–54. Bibcode:1997PNAS...94.7549R. doi:10.1073/pnas.94.14.7549. PMC23859. PMID 9207129.
^Liu H, Chen B, Li Y (March 2019). "microRNA-203 promotes proliferation, differentiation, and migration of osteoblasts by upregulation of Msh homeobox 2". Journal of Cellular Physiology. 234 (10): 17639–17648. doi:10.1002/jcp.28387. PMID 30854680. S2CID 73726197.
^Fujita T, Hayashida K, Shiba H, Kishimoto A, Matsuda S, Takeda K, Kawaguchi H, Kurihara H (August 2010). "The expressions of claudin-1 and E-cadherin in junctional epithelium". Journal of Periodontal Research. 45 (4): 579–82. doi:10.1111/j.1600-0765.2009.01258.x. PMID 20337884.
^Zhao Y, Yao J, Wu XP, Zhao L, Zhou YX, Zhang Y, You QD, Guo QL, Lu N (June 2015). "Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL-6/STAT3 signaling pathway". Molecular Carcinogenesis. 54 (Suppl 1): E81-93. doi:10.1002/mc.22182. PMID 24976450. S2CID 29685898.
^Yu Z, Yu W, Liu J, Wu D, Wang C, Zhang J, Zhao J (July 2018). "Lens-specific deletion of the Msx2 gene increased apoptosis by enhancing the caspase-3/caspase-8 signaling pathway". The Journal of International Medical Research. 46 (7): 2843–2855. doi:10.1177/0300060518774687. PMC6124292. PMID 29921154.
^Melville H, Wang Y, Taub PJ, Jabs EW (December 2010). "Genetic basis of potential therapeutic strategies for craniosynostosis". American Journal of Medical Genetics. Part A. 152A (12): 3007–15. doi:10.1002/ajmg.a.33703. PMID 21082653. S2CID 24424024.
^ abcZhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (May 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Molecular and Cellular Biology. 17 (5): 2920–32. doi:10.1128/mcb.17.5.2920. PMC232144. PMID 9111364.
Further readingedit
Suzuki M, Tanaka M, Iwase T, Naito Y, Sugimura H, Kino I (July 1993). "Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors". Biochemical and Biophysical Research Communications. 194 (1): 187–93. doi:10.1006/bbrc.1993.1802. hdl:10271/1007. PMID 7687426. S2CID 27890243.
Semenza GL, Wang GL, Kundu R (April 1995). "DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2". Biochemical and Biophysical Research Communications. 209 (1): 257–62. doi:10.1006/bbrc.1995.1497. PMID 7726844.
Iimura T (December 1994). "[Molecular cloning and expression of homeobox-containing genes during hard tissue development]". Kokubyo Gakkai Zasshi. The Journal of the Stomatological Society, Japan. 61 (4): 590–604. doi:10.5357/koubyou.61.590. PMID 7897272. S2CID 2781509.
Hodgkinson JE, Davidson CL, Beresford J, Sharpe PT (July 1993). "Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1174 (1): 11–6. doi:10.1016/0167-4781(93)90086-s. PMID 8101453.
Jabs EW, Müller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB (November 1993). "A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis". Cell. 75 (3): 443–50. doi:10.1016/0092-8674(93)90379-5. PMID 8106171. S2CID 13650758.
Ma L, Golden S, Wu L, Maxson R (December 1996). "The molecular basis of Boston-type craniosynostosis: the Pro148→His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences". Human Molecular Genetics. 5 (12): 1915–20. doi:10.1093/hmg/5.12.1915. PMID 8968743.
Quinn LM, Johnson BV, Nicholl J, Sutherland GR, Kalionis B (March 1997). "Isolation and identification of homeobox genes from the human placenta including a novel member of the Distal-less family, DLX4". Gene. 187 (1): 55–61. doi:10.1016/S0378-1119(96)00706-8. PMID 9073066.
Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (May 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Molecular and Cellular Biology. 17 (5): 2920–32. doi:10.1128/mcb.17.5.2920. PMC232144. PMID 9111364.
Wu L, Wu H, Ma L, Sangiorgi F, Wu N, Bell JR, Lyons GE, Maxson R (July 1997). "Miz1, a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA". Mechanisms of Development. 65 (1–2): 3–17. doi:10.1016/S0925-4773(97)00032-4. PMID 9256341. S2CID 11835268.
Stelnicki EJ, Kömüves LG, Holmes D, Clavin W, Harrison MR, Adzick NS, Largman C (October 1997). "The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin". Differentiation; Research in Biological Diversity. 62 (1): 33–41. doi:10.1046/j.1432-0436.1997.6210033.x. PMID 9373945.
Iimura T, Takeda K, Goseki M, Maruoka Y, Sasaki S, Oida S (1998). "Characterization of two length cDNA for human MSX-2 from dental pulp-derived cells". DNA Sequence. 8 (1–2): 87–92. doi:10.3109/10425179709020891. PMID 9522127.
Newberry EP, Latifi T, Towler DA (August 1999). "The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter". Biochemistry. 38 (33): 10678–90. doi:10.1021/bi990967j. PMID 10451362.
Wilkie AO, Tang Z, Elanko N, Walsh S, Twigg SR, Hurst JA, Wall SA, Chrzanowska KH, Maxson RE (April 2000). "Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification". Nature Genetics. 24 (4): 387–90. doi:10.1038/74224. PMID 10742103. S2CID 21030594.
Wuyts W, Reardon W, Preis S, Homfray T, Rasore-Quartino A, Christians H, Willems PJ, Van Hul W (May 2000). "Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna". Human Molecular Genetics. 9 (8): 1251–5. doi:10.1093/hmg/9.8.1251. PMID 10767351.
Quinn LM, Latham SE, Kalionis B (2000). "The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial-mesenchymal cell interactions in the human placenta". Placenta. 21 Suppl A (Suppl A): S50-4. doi:10.1053/plac.1999.0514. PMID 10831122.
Masuda Y, Sasaki A, Shibuya H, Ueno N, Ikeda K, Watanabe K (February 2001). "Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function". The Journal of Biological Chemistry. 276 (7): 5331–8. doi:10.1074/jbc.M008590200. PMID 11084035.
Shirakabe K, Terasawa K, Miyama K, Shibuya H, Nishida E (October 2001). "Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5". Genes to Cells. 6 (10): 851–6. doi:10.1046/j.1365-2443.2001.00466.x. PMID 11683913. S2CID 22071040.
External linksedit
GeneReviews/NCBI/UW/NIH entry on Enlarged Parietal Foramina/Cranium Bifidum
homeobox, homeobox, protein, protein, that, humans, encoded, msx2, gene, msx2identifiersaliasesmsx2, crs2, hox8, pfm1, external, idsomim, 123101, 97169, homologene, 1837, genecards, msx2gene, location, human, chromosome, human, band5q35, 2start174, end174, exp. Homeobox protein MSX 2 is a protein that in humans is encoded by the MSX2 gene 4 5 6 MSX2IdentifiersAliasesMSX2 CRS2 FPP HOX8 MSH PFM PFM1 Msh homeobox 2External IDsOMIM 123101 MGI 97169 HomoloGene 1837 GeneCards MSX2Gene location Human Chr Chromosome 5 human 1 Band5q35 2Start174 724 582 bp 1 End174 730 896 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed inplacentasecondary oocytelactiferous ducturinary bladdermucosa of urinary bladderskin of abdomengastrocnemius musclesmooth muscle tissueleft ventricleoptic nerven aMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionsequence specific DNA binding DNA binding transcription coregulator activity DNA binding transcription repressor activity RNA polymerase II specific RNA polymerase II transcription regulatory region sequence specific DNA binding protein binding transcription factor binding DNA binding transcription factor activity RNA polymerase II specificCellular componentnucleus cytosol nuclear speckBiological processnegative regulation of cell population proliferation positive regulation of timing of catagen negative regulation of keratinocyte differentiation negative regulation of transcription regulatory region DNA binding embryonic limb morphogenesis frontal suture morphogenesis mammary gland epithelium development BMP signaling pathway involved in heart development enamel mineralization ossification anterior posterior pattern specification bone morphogenesis regulation of transcription DNA templated cellular response to growth factor stimulus activation of meiosis endochondral bone growth wound healing spreading of epidermal cells BMP signaling pathway embryonic digit morphogenesis positive regulation of mesenchymal cell apoptotic process multicellular organism development embryonic hindlimb morphogenesis negative regulation of CREB transcription factor activity outflow tract morphogenesis bone trabecula formation wound healing regulation of apoptotic process chondrocyte development osteoblast development positive regulation of osteoblast differentiation cranial suture morphogenesis negative regulation of fat cell differentiation branching involved in mammary gland duct morphogenesis outflow tract septum morphogenesis negative regulation of transcription DNA templated osteoblast differentiation epithelial to mesenchymal transition involved in endocardial cushion formation positive regulation of BMP signaling pathway signal transduction involved in regulation of gene expression cellular response to estradiol stimulus embryonic forelimb morphogenesis embryonic nail plate morphogenesis negative regulation of apoptotic process cartilage development stem cell differentiation odontogenesis transcription DNA templated negative regulation of transcription by RNA polymerase II embryonic morphogenesisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez448817702EnsemblENSG00000120149n aUniProtP35548Q03358RefSeq mRNA NM 002449NM 001363626NM 013601RefSeq protein NP 002440NP 001350555NP 038629Location UCSC Chr 5 174 72 174 73 Mbn aPubMed search 2 3 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 References 4 Further reading 5 External linksFunction editThis gene encodes a member of the muscle segment homeobox gene family The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest derived cells required for proper craniofacial morphogenesis The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2 6 Msx2 is a homeobox gene localized on human chromosome 5 that encodes a transcription repressor and activator MSX 2 responsible for craniofacial and limb bud development Cells will express msx2 when exposed to signaling molecules BMP 2 and BMP 4 in situ 7 Expression of msx2 leads to the proliferation migration and osteogenic differentiation of neural crest cells during embryogenesis and bone fracture 8 It is well documented that expression of cell cell adhesion molecules such as E cadherins will promote structural integrity and an epithelial arrangement of cells while expression of N cadherin and vimentin promote mesenchymal arrangement and cell migration 9 10 Msx2 downregulates E cadherins and upregulates N cadherin and vimentin which indicates its role in inducing epithelial mesenchymal transition EMT Germline knockout mice have been created for this gene Msx2 in order to examine functional loss 11 Clinical studies on craniosynostosis or the premature fusion of cranial structures have shown the condition to be genetically linked to mutation in the msx2 homeobox gene 12 Interactions editMsh homeobox 2 has been shown to interact with DLX5 13 DLX2 13 and MSX1 13 References edit a b c GRCh38 Ensembl release 89 ENSG00000120149 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Takahashi C Akiyama N Matsuzaki T Takai S Kitayama H Noda M May 1996 Characterization of a human MSX 2 cDNA and its fragment isolated as a transformation suppressor gene against v Ki ras oncogene Oncogene 12 10 2137 46 PMID 8668339 Kostrzewa M Grady DL Moyzis RK Floter L Muller U March 1996 Integration of four genes a pseudogene thirty one STSs and a highly polymorphic STRP into the 7 10 Mb YAC contig of 5q34 q35 Human Genetics 97 3 399 403 doi 10 1007 BF02185781 PMID 8786091 S2CID 12647370 a b Entrez Gene MSX2 msh homeobox 2 Rifas L July 1997 Gestational exposure to ethanol suppresses msx2 expression in developing mouse embryos Proc Natl Acad Sci U S A 94 14 7549 54 Bibcode 1997PNAS 94 7549R doi 10 1073 pnas 94 14 7549 PMC 23859 PMID 9207129 Liu H Chen B Li Y March 2019 microRNA 203 promotes proliferation differentiation and migration of osteoblasts by upregulation of Msh homeobox 2 Journal of Cellular Physiology 234 10 17639 17648 doi 10 1002 jcp 28387 PMID 30854680 S2CID 73726197 Fujita T Hayashida K Shiba H Kishimoto A Matsuda S Takeda K Kawaguchi H Kurihara H August 2010 The expressions of claudin 1 and E cadherin in junctional epithelium Journal of Periodontal Research 45 4 579 82 doi 10 1111 j 1600 0765 2009 01258 x PMID 20337884 Zhao Y Yao J Wu XP Zhao L Zhou YX Zhang Y You QD Guo QL Lu N June 2015 Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL 6 STAT3 signaling pathway Molecular Carcinogenesis 54 Suppl 1 E81 93 doi 10 1002 mc 22182 PMID 24976450 S2CID 29685898 Yu Z Yu W Liu J Wu D Wang C Zhang J Zhao J July 2018 Lens specific deletion of the Msx2 gene increased apoptosis by enhancing the caspase 3 caspase 8 signaling pathway The Journal of International Medical Research 46 7 2843 2855 doi 10 1177 0300060518774687 PMC 6124292 PMID 29921154 Melville H Wang Y Taub PJ Jabs EW December 2010 Genetic basis of potential therapeutic strategies for craniosynostosis American Journal of Medical Genetics Part A 152A 12 3007 15 doi 10 1002 ajmg a 33703 PMID 21082653 S2CID 24424024 a b c Zhang H Hu G Wang H Sciavolino P Iler N Shen MM Abate Shen C May 1997 Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism Molecular and Cellular Biology 17 5 2920 32 doi 10 1128 mcb 17 5 2920 PMC 232144 PMID 9111364 Further reading editSuzuki M Tanaka M Iwase T Naito Y Sugimura H Kino I July 1993 Over expression of HOX 8 the human homologue of the mouse Hox 8 homeobox gene in human tumors Biochemical and Biophysical Research Communications 194 1 187 93 doi 10 1006 bbrc 1993 1802 hdl 10271 1007 PMID 7687426 S2CID 27890243 Semenza GL Wang GL Kundu R April 1995 DNA binding and transcriptional properties of wild type and mutant forms of the homeodomain protein Msx2 Biochemical and Biophysical Research Communications 209 1 257 62 doi 10 1006 bbrc 1995 1497 PMID 7726844 Iimura T December 1994 Molecular cloning and expression of homeobox containing genes during hard tissue development Kokubyo Gakkai Zasshi The Journal of the Stomatological Society Japan 61 4 590 604 doi 10 5357 koubyou 61 590 PMID 7897272 S2CID 2781509 Hodgkinson JE Davidson CL Beresford J Sharpe PT July 1993 Expression of a human homeobox containing gene is regulated by 1 25 OH 2D3 in bone cells Biochimica et Biophysica Acta BBA Gene Structure and Expression 1174 1 11 6 doi 10 1016 0167 4781 93 90086 s PMID 8101453 Jabs EW Muller U Li X Ma L Luo W Haworth IS Klisak I Sparkes R Warman ML Mulliken JB November 1993 A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis Cell 75 3 443 50 doi 10 1016 0092 8674 93 90379 5 PMID 8106171 S2CID 13650758 Ma L Golden S Wu L Maxson R December 1996 The molecular basis of Boston type craniosynostosis the Pro148 His mutation in the N terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences Human Molecular Genetics 5 12 1915 20 doi 10 1093 hmg 5 12 1915 PMID 8968743 Quinn LM Johnson BV Nicholl J Sutherland GR Kalionis B March 1997 Isolation and identification of homeobox genes from the human placenta including a novel member of the Distal less family DLX4 Gene 187 1 55 61 doi 10 1016 S0378 1119 96 00706 8 PMID 9073066 Zhang H Hu G Wang H Sciavolino P Iler N Shen MM Abate Shen C May 1997 Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism Molecular and Cellular Biology 17 5 2920 32 doi 10 1128 mcb 17 5 2920 PMC 232144 PMID 9111364 Wu L Wu H Ma L Sangiorgi F Wu N Bell JR Lyons GE Maxson R July 1997 Miz1 a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA Mechanisms of Development 65 1 2 3 17 doi 10 1016 S0925 4773 97 00032 4 PMID 9256341 S2CID 11835268 Newberry EP Latifi T Battaile JT Towler DA August 1997 Structure function analysis of Msx2 mediated transcriptional suppression Biochemistry 36 34 10451 62 doi 10 1021 bi971008x PMID 9265625 Stelnicki EJ Komuves LG Holmes D Clavin W Harrison MR Adzick NS Largman C October 1997 The human homeobox genes MSX 1 MSX 2 and MOX 1 are differentially expressed in the dermis and epidermis in fetal and adult skin Differentiation Research in Biological Diversity 62 1 33 41 doi 10 1046 j 1432 0436 1997 6210033 x PMID 9373945 Iimura T Takeda K Goseki M Maruoka Y Sasaki S Oida S 1998 Characterization of two length cDNA for human MSX 2 from dental pulp derived cells DNA Sequence 8 1 2 87 92 doi 10 3109 10425179709020891 PMID 9522127 Newberry EP Latifi T Towler DA August 1999 The RRM domain of MINT a novel Msx2 binding protein recognizes and regulates the rat osteocalcin promoter Biochemistry 38 33 10678 90 doi 10 1021 bi990967j PMID 10451362 Wilkie AO Tang Z Elanko N Walsh S Twigg SR Hurst JA Wall SA Chrzanowska KH Maxson RE April 2000 Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification Nature Genetics 24 4 387 90 doi 10 1038 74224 PMID 10742103 S2CID 21030594 Wuyts W Reardon W Preis S Homfray T Rasore Quartino A Christians H Willems PJ Van Hul W May 2000 Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna Human Molecular Genetics 9 8 1251 5 doi 10 1093 hmg 9 8 1251 PMID 10767351 Quinn LM Latham SE Kalionis B 2000 The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial mesenchymal cell interactions in the human placenta Placenta 21 Suppl A Suppl A S50 4 doi 10 1053 plac 1999 0514 PMID 10831122 Masuda Y Sasaki A Shibuya H Ueno N Ikeda K Watanabe K February 2001 Dlxin 1 a novel protein that binds Dlx5 and regulates its transcriptional function The Journal of Biological Chemistry 276 7 5331 8 doi 10 1074 jbc M008590200 PMID 11084035 Shirakabe K Terasawa K Miyama K Shibuya H Nishida E October 2001 Regulation of the activity of the transcription factor Runx2 by two homeobox proteins Msx2 and Dlx5 Genes to Cells 6 10 851 6 doi 10 1046 j 1365 2443 2001 00466 x PMID 11683913 S2CID 22071040 External links editGeneReviews NCBI UW NIH entry on Enlarged Parietal Foramina Cranium Bifidum MSX2 protein human at the U S National Library of Medicine Medical Subject Headings MeSH MSX2 human gene location in the UCSC Genome Browser MSX2 human gene details in the UCSC Genome Browser This article incorporates text from the United States National Library of Medicine which is in the public domain nbsp This article on a gene on human chromosome 5 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Msh homeobox 2 amp oldid 1223731010, wikipedia, wiki, book, books, library,
