Hh in Drosophila and its Homologues

Hh protein is activated through carboxy-terminal cleavage and simultaneous covalent attachment of cholesterol, leading to post-translational modifications. Mammalian homologues undergo similar reactions.

Mechanisms surrounding Hh have been slowly clarified by studies in other genes such as Drosophoila's dispatched (disp) gene , required in Hh expressing cells. The disp protein is phylogenetically related to protein families with a sterol-sensing domain (SSD), one of these being the patched (ptc) protein. This indicates that cholesterol plays an important role in the Hh signalling pathway. The role of cholesterol attachment in Hh signalling is as yet unknown.

Cells that make the vertebrate Hh have also displayed functions of disp in sequence homologues of disp in vertebrate.

Sonic Hedgehog

Sonic Hedgehog (Shh, the biochemical and functional homologue of hedgehog in vertebrate) is involved with developmental patterning events, specifically for polarization of the anterior-posterior axis of the developing limb-bud.

Roles of Shh in vertebrates include determining the anterior-posterior patterning of limbs, determining dorsal ventral polarity of the neural tube, determining body symmetry and in development of the gut.

Fish contain additional hedgehog genes: echidna hedgehog and tiggywinkle hedgehog. These are both expressed in the midline of fish embryo and interact with Shh to establish cell fates of midline cells.

Indian Hedgehog

Research into Indian Hedgehog (Ihh) has revealed its involvement in vertebrate development of both the endoderm (differentiation of the visceral endoderm) and proliferation and differentiation of gut epithelial stem cells. Both Shh and Ihh are required for gut development.

Desert Hedgehog

Desert Hedgehog (Dhh) is important in both the male germline and in differentiation of glial cells. Its roles include peripheral nerve sheath development and spermatogenesis. Dhh encodes a signalling molecule found only in the testis (not in the ovary), and Dhh expression initiates in Sertoli cell precursors (Sertoli cells are specific to interactions in the male germline). In the nervous system, a sheath is formed around peripheral nerves through signals from Schwann cell-derived Dhh. Dhh mRNA is expressed in Schwann cells.