Sonic Hedgehog - Function

Function

Of the hh homologues, shh has been found to have the most critical roles in development, acting as a morphogen involved in patterning many systems, including the limb and midline structures in the brain, spinal cord, the thalamus by the zona limitans intrathalamica and the teeth. Mutations in the human sonic hedgehog gene, SHH, cause holoprosencephaly type 3 (HPE3) as a result of the loss of the ventral midline. Sonic hedgehog is secreted at the zone of polarizing activity (ZPA), which is located on posterior side of a limb bud in an embryo. The sonic hedgehog transcription pathway has also been linked to the formation of specific kinds of cancerous tumours.

More recently, sonic hedgehog has also been shown to act as an axonal guidance cue. It has been demonstrated that Shh attracts commissural axons at the ventral midline of the developing spinal cord. Specifically, Shh attracts retinal ganglion cell (RGC) axons at low concentrations and repels them at higher concentrations. The absence (non-expression) of Shh has been shown to control the growth of nascent hind limbs in cetaceans (whales and dolphins).

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