Sonic hedgehog.

segment polarity genes that regulate segmental and imaginal disc patterning in the fruit fly, Drosophila melanogaster. Unlike drosophila and other invertebrates, which only have a single hh gene, vertebrates have a family of genes that are homologous to the hh gene. Mammals have three genes with homology to the hh gene. These comprise Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). All hedgehog genes encode signalling molecules that are involved in short and long range patterning processes during embryogenesis. Like all hedgehog proteins Shh protein also undergoes molecular processing in the endoplasmic reticulum. This involves cleavage of its signal peptide, followed by autocatalytic cleavage of the hedgehog protein precursor into a 19 kDa N-terminal domain (Shh-N) and a 25 kDa C-terminal domain (Shh-C). The signalling activity of hedgehog proteins resides in Shh-N. Shh-C has intramolecular cholesterol transferase activity and is responsible for covalently attaching a cholesterol molecule to the C-terminal end of Shh-N. The addition of cholesterol plays an important role in spatially restricting the zone of activity of Shh-N by anchoring it to the cell membrane and restricting its diffusion from the site of secretion. It is believed that inborn errors of cholesterol synthesis such as Smith–Lemli–Opitz syndrome (microcephaly, growth and mental retardation, facial dysmorphism, syndactyly of the second and third toes, congenital heart disease, hypotonia, and genital abnormalities in males) can interfere with SHH signalling by interfering with its molecular processing, in particular with the cholesterol modification of Shh-N.