Indian hedgehog (protein) explained

Indian hedgehog homolog (Drosophila), also known as IHH, is a protein which in humans is encoded by the IHH gene.[1] [2] [3] This cell signaling protein is in the hedgehog signaling pathway. The several mammalian variants of the Drosophila hedgehog gene (which was the first named) have been named after the various species of hedgehog; the Indian hedgehog is honored by this one. The gene is not specific to Indian hedgehogs.

Function

The Indian hedgehog protein is one of three proteins in the mammalian hedgehog family, the others being desert hedgehog (DHH) and sonic hedgehog (SHH).[4] It is involved in chondrocyte differentiation, proliferation and maturation especially during endochondral ossification. It regulates its effects by feedback control of parathyroid hormone-related peptide (PTHrP).[5]

Indian Hedge Hog, (Ihh) is one of three signaling molecules from the Hedgehog (Hh) gene family.[6] Genes of the Hh family, Sonic Hedgehog (Shh), Desert Hedgehog (Dhh) and Ihh regulate several fetal developmental processes. The Ihh homolog is involved in the formation of chondrocytes during the development of limbs. The protein is released by small, non-proliferating, mature chondrocytes during endochondral ossification. Recently, Ihh mutations are shown to cause brachydactyly type A1 (BDA1), the first Mendelian autosomal dominant disorder in humans to be recorded.[7] There are seven known mutations to Ihh that cause BDA1. Of particular interest, are mutations involving the E95 residue, which is thought to be involved with proper signaling mechanisms between Ihh and its receptors. In a mouse model, mice with mutations to the E95 residue were found to have abnormalities to their digits.[8]

Ihh may also be involved in endometrial cell differentiation and implantation. Studies have shown progesterone to upregulate Ihh expression in the murine endometrium, suggesting a role in implantation.[9] Ihh is suspected to be involved in the downstream regulation of other signaling molecules that are known to play a role in murine implantation.[10] Mouse models involving Ihh null mice demonstrated failure of attachment and decidualization.

Further reading

Notes and References

  1. Web site: Entrez Gene: IHH Indian hedgehog homolog (Drosophila).
  2. Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE . Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog . Genomics . 28 . 1 . 44–51 . July 1995 . 7590746 . 10.1006/geno.1995.1104 .
  3. van den Brink GR, Bleuming SA, Hardwick JC, Schepman BL, Offerhaus GJ, Keller JJ, Nielsen C, Gaffield W, van Deventer SJ, Roberts DJ, Peppelenbosch MP . Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation . Nat. Genet. . 36 . 3 . 277–82 . March 2004 . 14770182 . 10.1038/ng1304 . free .
  4. Kumar S, Balczarek KA, Lai ZC . Evolution of the hedgehog gene family . Genetics . 142 . 3 . 965–72 . March 1996 . 10.1093/genetics/142.3.965 . 8849902 . 1207033 .
  5. Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ . Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein . Science . 273 . 5275 . 613–22 . August 1996 . 8662546 . 10.1126/science.273.5275.613 . 1996Sci...273..613V . 27737023 .
  6. Ma, G., Yu, J., Xiao, Y. et al. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. Cell Res 21, 1343–1357 (2011). https://doi.org/10.1038/cr.2011.76
  7. Lodder EM, Hoogeboom AJM, Coert JH, de Graaff E. 2008. Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1. Am J Med Genet Part A 146A:2152–2154. doi:10.1002/ajmg.a.32441
  8. Gao, B., Hu, J., Stricker, S. et al. A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range. Nature 458, 1196–1200 (2009). https://doi.org/10.1038/nature07862
  9. Qingxiang Wei, Eric D. Levens, Lilja Stefansson, Lynnette K. Nieman, Indian Hedgehog and Its Targets in Human Endometrium: Menstrual Cycle Expression and Response to CDB-2914, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 12, 1 December 2010, Pages 5330–5337, https://doi.org/10.1210/jc.2010-0637
  10. Kathryn Smith, Redab Alnifaidy, Qingxiang Wei, Lynnette K. Nieman, Endometrial Indian hedgehog expression is decreased in women with endometriosis, Fertility and Sterility, Volume 95, Issue 8, 2011, Pages 2738-2741.e3, ISSN 0015-0282, https://doi.org/10.1016/j.fertnstert.2011.05.018.

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