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Gene Review

Msx1  -  msh homeobox 1

Mus musculus

Synonyms: AA675338, AI324650, Homeobox protein Hox-7, Homeobox protein MSX-1, Hox-7, ...
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Disease relevance of Msx1

  • The Msx1 gene controls many aspects of craniofacial development, as evidenced by craniofacial abnormalities seen in Msx1(-/-) mice, including the arrest of tooth development and the absence of the alveolar bone [1].
  • Homozygous mutant mice die at birth with facial defects (see Satokata, I. and Maas, R. (1994) Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nat. Genet. 6, 348-356) [2].
  • These data establish that Lmx1a and Msx1 are critical intrinsic dopamine-neuron determinants in vivo and suggest that they may be essential tools in cell replacement strategies in Parkinson's disease [3].

High impact information on Msx1


Chemical compound and disease context of Msx1


Biological context of Msx1

  • Moreover, in contrast to the tooth bud stage arrest observed in Msx1 mutants, Msx1,Msx2 double mutants exhibit an earlier phenotype closely resembling the lamina stage arrest observed in Dlx1,Dlx2 double mutants [8].
  • Msx1 expression was investigated in the context of the onset of dermis formation monitored by the Dermo1 gene expression [9].
  • Msx1 controls inductive signaling in mammalian tooth morphogenesis [10].
  • In the underlying mesenchyme of AER-free areas, cell proliferation was reduced, and transcription of Shh and Msx1 was diminished [11].
  • Taking advantage of an nlacZ reporter gene integrated into the mouse Msx1 locus (Msx1(nlacZ) allele), we detected segmental expression of the Msx1 gene in cells of the dorsal mesenchyme of the trunk between embryonic days 11 and 14 [9].

Anatomical context of Msx1

  • Early expression of Islet1 in presumptive incisor epithelium is coincident with expression of Bmp4, which acts to induce Msx1 expression in the underlying mesenchyme [12].
  • Cells expressing the Msx1 gene would migrate from the somite and contribute to the dermis of the dorsalmost trunk region [9].
  • To further analyze the role of Msx1 in regulating epithelial-mesenchymal interactions during tooth morphogenesis, we have examined the expression of several potential Msx1 downstream genes in Msx1 mutant tooth germs and we have performed functional experiments designed to order these genes into a pathway [10].
  • The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites [9].
  • The gene is downregulated prior to the onset of dermis differentiation, suggesting a role for Msx1 in the control of this process [9].

Associations of Msx1 with chemical compounds

  • Regardless of cholesterol content, high fat diets induced mineralization of the proximal aorta (assessed by von Kossa staining) and promoted aortic expression of Msx2 and Msx1, genes encoding homeodomain transcription factors that regulate mineralization and osseous differentiation programs in the developing skull [13].
  • The gradients of Msx1 and Neuropilin-2 expression in basal cells and neurons, respectively, correlated with expression of a retinoic acid-synthesizing enzyme (RALDH2) in lamina propria [14].
  • Histologic sections showed that progenitor as well as differentiating and differentiated cells of all the bone cell lineages could express the Msx1 protein (chondrocytes, osteoblasts, tartrate-resistant acid phosphatase positive osteoclasts and chondroclasts) [15].
  • Utilizing a series of truncated Msx-1 polypeptides, we show that multiple regions of Msx-1 contribute to repression, and these are rich in alanine, glycine, and proline residues [16].
  • Importantly, a perfect reverse complement of (C/G)TTAATTG, which was recently shown to be an optimal binding sequence for the homeodomain of Msx-1 protein (K.M. Catron, N. Iler, and C. Abate (1993) Mol. Cell. Biol. 13:2354-2365), was also located in the murine Msx-1 promoter [17].

Physical interactions of Msx1


Co-localisations of Msx1

  • In addition, Id colocalizes both spatially and temporally with Hox-7.1, a murine homeobox gene which is associated with regions of high cell proliferation and positional fate assignment [19].

Regulatory relationships of Msx1


Other interactions of Msx1

  • However, the expression of three molecules involved in tooth initiation, Bmp4, Msx1, and Msx2, are absent from the presumptive chick dental lamina [23].
  • These results are consistent with functional redundancy between Msx1 and Msx2 in dental mesenchyme and support a model whereby Msx and Dlx genes function in parallel within the dental mesenchyme during tooth initiation [8].
  • Moreover, dental epithelium as well as beads soaked in FGF1, FGF2 or FGF8 induce Fgf3 expression in dental mesenchyme in an Msx1-dependent manner [8].
  • In the latter case, the absence of Dlx5 rescues in part the Msx1-dependent defects in palate growth and elevation [24].
  • We conclude that in the context of the tooth germ Msx1 is a component of the Shh signaling pathway that leads to Ptc induction [25].

Analytical, diagnostic and therapeutic context of Msx1


  1. Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via induction of Dlx5 and Cbfa1. Zhang, Z., Song, Y., Zhang, X., Tang, J., Chen, J., Chen, Y. Mech. Dev. (2003) [Pubmed]
  2. Insertional mutation of the mouse Msx1 homeobox gene by an nlacZ reporter gene. Houzelstein, D., Cohen, A., Buckingham, M.E., Robert, B. Mech. Dev. (1997) [Pubmed]
  3. Identification of intrinsic determinants of midbrain dopamine neurons. Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., Ericson, J. Cell (2006) [Pubmed]
  4. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Satokata, I., Ma, L., Ohshima, H., Bei, M., Woo, I., Nishizawa, K., Maeda, T., Takano, Y., Uchiyama, M., Heaney, S., Peters, H., Tang, Z., Maxson, R., Maas, R. Nat. Genet. (2000) [Pubmed]
  5. MSX1 inhibits myoD expression in fibroblast x 10T1/2 cell hybrids. Woloshin, P., Song, K., Degnin, C., Killary, A.M., Goldhamer, D.J., Sassoon, D., Thayer, M.J. Cell (1995) [Pubmed]
  6. Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Satokata, I., Maas, R. Nat. Genet. (1994) [Pubmed]
  7. MSX-1 gene expression and regulation in embryonic palatal tissue. Nugent, P., Greene, R.M. In Vitro Cell. Dev. Biol. Anim. (1998) [Pubmed]
  8. FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Bei, M., Maas, R. Development (1998) [Pubmed]
  9. The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites. Houzelstein, D., Chéraud, Y., Auda-Boucher, G., Fontaine-Pérus, J., Robert, B. Development (2000) [Pubmed]
  10. Msx1 controls inductive signaling in mammalian tooth morphogenesis. Chen, Y., Bei, M., Woo, I., Satokata, I., Maas, R. Development (1996) [Pubmed]
  11. Novel roles of Fgfr2 in AER differentiation and positioning of the dorsoventral limb interface. Gorivodsky, M., Lonai, P. Development (2003) [Pubmed]
  12. Role of Islet1 in the patterning of murine dentition. Mitsiadis, T.A., Angeli, I., James, C., Lendahl, U., Sharpe, P.T. Development (2003) [Pubmed]
  13. Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice. Towler, D.A., Bidder, M., Latifi, T., Coleman, T., Semenkovich, C.F. J. Biol. Chem. (1998) [Pubmed]
  14. Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map. Norlin, E.M., Alenius, M., Gussing, F., Hägglund, M., Vedin, V., Bohm, S. Mol. Cell. Neurosci. (2001) [Pubmed]
  15. Postnatal Msx1 expression pattern in craniofacial, axial, and appendicular skeleton of transgenic mice from the first week until the second year. Orestes-Cardoso, S.M., Nefussi, J.R., Hotton, D., Mesbah, M., Orestes-Cardoso, M.D., Robert, B., Berdal, A. Dev. Dyn. (2001) [Pubmed]
  16. Transcriptional repression by Msx-1 does not require homeodomain DNA-binding sites. Catron, K.M., Zhang, H., Marshall, S.C., Inostroza, J.A., Wilson, J.M., Abate, C. Mol. Cell. Biol. (1995) [Pubmed]
  17. Murine homeobox-containing gene, Msx-1: analysis of genomic organization, promoter structure, and potential autoregulatory cis-acting elements. Kuzuoka, M., Takahashi, T., Guron, C., Raghow, R. Genomics (1994) [Pubmed]
  18. SMAD 8 binding to mice Msx1 basal promoter is required for transcriptional activation. Binato, R., Alvarez Martinez, C.E., Pizzatti, L., Robert, B., Abdelhay, E. Biochem. J. (2006) [Pubmed]
  19. Id expression during mouse development: a role in morphogenesis. Wang, Y., Benezra, R., Sassoon, D.A. Dev. Dyn. (1992) [Pubmed]
  20. Msx1 is required for dorsal diencephalon patterning. Bach, A., Lallemand, Y., Nicola, M.A., Ramos, C., Mathis, L., Maufras, M., Robert, B. Development (2003) [Pubmed]
  21. Msx1 (Hox-7.1) in the adult mouse uterus: cellular interactions underlying regulation of expression. Pavlova, A., Boutin, E., Cunha, G., Sassoon, D. Development (1994) [Pubmed]
  22. Msx1-deficient mice fail to form prosomere 1 derivatives, subcommissural organ, and posterior commissure and develop hydrocephalus. Fernández-Llebrez, P., Grondona, J.M., Pérez, J., López-Aranda, M.F., Estivill-Torrús, G., Llebrez-Zayas, P.F., Soriano, E., Ramos, C., Lallemand, Y., Bach, A., Robert, B. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  23. Conservation of early odontogenic signaling pathways in Aves. Chen, Y., Zhang, Y., Jiang, T.X., Barlow, A.J., St Amand, T.R., Hu, Y., Heaney, S., Francis-West, P., Chuong, C.M., Maas, R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  24. Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation. Levi, G., Mantero, S., Barbieri, O., Cantatore, D., Paleari, L., Beverdam, A., Genova, F., Robert, B., Merlo, G.R. Mech. Dev. (2006) [Pubmed]
  25. Msx1 is required for the induction of Patched by Sonic hedgehog in the mammalian tooth germ. Zhang, Y., Zhao, X., Hu, Y., St Amand, T., Zhang, M., Ramamurthy, R., Qiu, M., Chen, Y. Dev. Dyn. (1999) [Pubmed]
  26. Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice. Reginelli, A.D., Wang, Y.Q., Sassoon, D., Muneoka, K. Development (1995) [Pubmed]
  27. Necdin interacts with the Msx2 homeodomain protein via MAGE-D1 to promote myogenic differentiation of C2C12 cells. Kuwajima, T., Taniura, H., Nishimura, I., Yoshikawa, K. J. Biol. Chem. (2004) [Pubmed]
  28. Msx1 expression in the adult mouse brain: characterization of populations of beta-galactosidase-positive cells in the hippocampus and fimbria. Ramos, C., Martinez, A., Robert, B., Soriano, E. Neuroscience (2004) [Pubmed]
  29. Msx1 homeogene antisense mRNA in mouse dental and bone cells. Berdal, A., Lezot, F., Pibouin, L., Hotton, D., Ghoul-Mazgar, S., Teillaud, C., Robert, B., MacDougall, M., Blin, C. Connect. Tissue Res. (2002) [Pubmed]
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