Hedgehog (Hh) proteins encode a family of secreted signalling molecules that regulates cell development, functioning anteroposterior patterning and differentiation (including organ systems) of cell types in various species. Hh was initially identified as being required for segmentation of the Drosophila embryo and has since been recognised in other areas of embryonic, larval and adult development in the fly, in addition to developmental processes in other species such as human, frog, mouse and fish.
Absence or decrease in activity of the Hh signalling pathway can lead to serious developmental birth defects, including holopresencephaly - malformation of the brain and head. Basal Cell Carcinomas and other human cancers have also been associated with the unscheduled activation of the Hh signalling pathway following genetic studies.
Hh controls the process of transcription of specific target genes in responsive cells through a transduction mechanism. By opposing a repressor system, Hh protein induces transcription of the target genes, encoding the secondary signals, including wingless (wg) and decapentaplegic (dpp). The repressors are Costal2 (Cos2), protein kinase A (Pka) and the Hh receptor patched (ptc).
Fused (fu) a kinase and Cubitus Interrupts (Ci) a transcription factor act positively on targets in the pathway, as does the Hh protein. Initiation occurs through activity of zinc finger transcription factors of Cubitus interrupts (Ci) / GLI family.
The active signalling form of Hh (HH-N) is covalently attached to cholesterol, which influences the range of Hh signalling.
The name 'hedgehog' is derived from spiky processes called denticles that cover the larval cuticle in Hh homozygotes. Most segment polarity classes share this feature and suggest that segment polarity genes function in a common pathway, in addition, most are involved in either Hh signal transduction or signalling by the wg gene.
