The gene hedgehog is one of the most important embryonic signaling molecules known. Like so many genes, the discovery of hedgehog in fruit flies led to the discovery of its homolog in vertebrates, which was named Sonic hedgehog (SHH). The role of hedgehog homologs in the development of the nervous system and eyes in both vertebrates and invertebrates supports that these genetic mechanisms were in place in the ancestor of the coelomates.

During the embryonic development of vertebrates (including humans), Sonic hedgehog is expressed in the notochord and ventral portions of the spinal cord, where provides the embryonic cells with positional information regarding their position in the developing body. The neural tube and notochord of the developing chick are depicted below.

neural tube

On the right side of the heart, SHH is suppressed and this helps to establish the asymmetric structure of the heart. Humans with SHH mutations are as likely to have their hearts on the right side of the sternum as the left. In vertebrates Shh controls the dorsal-ventral differentiation of the nervous system, the formation of left-right asymmetry, the formation of limb buds, and the development of the limb. Sonic hedgehog from the urethral epithelium is required for the development of the external genetalia. Interrupting Formin regulation of Shh can cause the absence of a thumb, fusion of 3rd and 4th digits, and radio-ulnar syntosis. Shh is involved in the elongation of digits and misexpression of Shh can cause a duplication of the digits. The developing arm of an embryonic pig is depicted below.

pig limb

The reduction of Shh and the resulting death of neural crest cells are responsible for some of the abnormalities of fetal alcohol exposure (Ahlgren, 2002).
SHH mutations can cause holoprosencephaly which is a common embryonic defect (affecting 1/250 embryos) and usually results in miscarriage (and thus affects 1/15,000 live births). It can cause a variety of defects ranging from the severe state of a single eye with a proboscis-like structure projecting from the forehead to milder defects including a single nostril, cleft lip, and a single central incisor.

human fetus with birth defect