You are here

Draft 39

Submitted by dfmiller on Thu, 11/21/2019 - 20:48

MSX2 inhibits the promoter sequence of amelogenin, antagonizing downstream C/EBPα as well as DLX2. This pathway is illustrated in figure 1. In the heterozygous mutant, decreased transcriptional repressor activity of MSX2 ultimately results in increased amelogenin expression.2 This increase of expressed amelogenin in the developing tooth ultimately results in increased enamel thickness, as well as increased rod size.2 In figure 2, Molla et al. analyzed 3 month postnatal mice with the wild type, heterozygous, and homozygous mutations. Molla et al. measured a 1.3-fold increase in enamel thickness2 in Msx2+/- mutants compared to the wild type. Of course, this Msx2+/– mutation is not a reliably heritable trait, and therefore a consistent observation of this phenotype among Homo Lontra populations must be the result of a cis-regulatory mutation, specifically within MSX2 enhancers. MSX2 contains a BMP-responsive enhancer sequence3, and a subsequent mutation within this enhancer sequence in Homo Lontra was found to result in the similar phenotype to Msx2+/– mutants.

  1. Li, J., Parada, C., & Chai, Y. (2017). Cellular and molecular mechanisms of tooth root development. Development, 144(3), 374–384. doi: 10.1242/dev.137216
  2. Molla, M., Descroix, V., Aïoub, M., Simon, S., Castañeda, B., Hotton, D., … Berdal, A. (2010). Enamel Protein Regulation and Dental and Periodontal Physiopathology in Msx2 Mutant Mice. The American Journal of Pathology, 177(5), 2516–2526. doi: 10.2353/ajpath.2010.091224
  3. Brugger, S. M., Merrill, A., Torres-Vazquez, J., Wu, N., Ting, M., Cho, J., … Maxson, R. (2004). A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development, 131(20), 5153–5165. doi: 10.1242/dev.01390