Recombinant Human Indian Hedgehog

The hedgehog (hh) gene encoding a secreted protein was originally identified in Drosophila as a segment polarity gene. The vertebrate homologues of Hh comprise several proteins including sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh) ^[1]. Hedgehog proteins are important signaling molecules during embryonic development and are highly conserved within and across species ^[1]. Mouse and human Ihh share 100% amino acid identity in the signaling domain, while mouse Ihh and Shh share 90% amino acid identity in the N-terminal signaling domain. Ihh mRNA expression is detected in fetal lung, gut, stomach, liver, kidney, pancreas and strongly in cartilage - in growth regions of the developing bone ^{[2, 3]}. Ihh, along with parathyroid hormone related protein, regulate the rate of chondrocyte proliferation and differentiation ^[4]. Ihh is also involved in yolk sac vasculogenesis, playing an important role in differentiation of epiblast cells into endothelial and red blood cells ^[5]. Mouse Ihh cDNA encodes a 411 amino acid (aa) polypeptide with a predicted 27 aa signal peptide. This polypeptide is cleaved to generate a 45 kDa precursor protein that undergoes the same post-translation processing as Shh ^[3]. An autocatalytic reaction yields a 19 kDa amino-terminal domain Ihh-N protein that retains all known signaling capabilities, and a 23 kDa carboxy-terminal domain Ihh-C protein ^[3]. Since hydrophobic modifications to Shh, including the substitution of the N-terminal cysteine residue with two hydrophobic isoleucine residues, can also increase its potency ^[6], a similar modification was made for Ihh. This modified form also shows increased potency in a bioassay measuring induction of alkaline phosphatase. At the cell surface, Hedgehog activity is mediated by a multicomponent receptor complex involving the 12-pass transmembrane protein Patched (Ptc) which binds Hedgehogs with high affinity and Smoothened (Smo), a signaling seven transmembrane G-protein coupled receptor ^[1].

Reference

[1]. Ingham, P. and A. McMahon (2001) Genes & Dev. 15:3059.

[2]. Marigo, V. et al. (1995) Genomics 28:44.

[3]. Valentini, R.P. et al. (1997) J Biol Chem. 272:8466.

[4]. Vortkamp, A. et al. (1996) Science 273:613.

[5]. Byrd, N. et al. (2002) Development 129:361.

[6]. Taylor, F.R. et al. (2001) Biochemistry 40: 4359.