Recombinant Human Desert Hedgehog/Dhh (C23II) N-Terminus, CF

Desert Hedgehog (Dhh) belongs to the highly conserved Hedgehog family of proteins which are involved in multiple developmental processes. Desert Hedgehog is a secreted, 45 kDa, 373 amino acid (aa) protein that undergoes autocatalytic cleavage between Gly198 and Cys199 catalyzed by the C-terminal domain, which releases the N-terminal domain with a concominant attachment of cholesterol at its new C-terminus. In addition to the C-terminally attached cholesterol, a fatty acid acyl chain is esterified to the N-terminal cysteine (aa 23) via an amide linkage. The 19 kDa N-terminal signaling domain is membrane associated due to its double lipid modifications. Its binding to Patched receptors results in the loss of Patched repression of Smoothened signaling (1 - 4). Dhh binds both Patched and Patched 2 as well as Hedgehog interacting protein (Hip) (5). Within the N-terminal domain, human Dhh shares 97% aa sequence identity with mouse and rat Dhh. It shares approximately 75% aa seqeuence identity with human Indian (Ihh) and Sonic Hedgehog (Shh) (5). Dhh is produced by Sertoli cells and is required for testis development and spermatogenesis (6, 7). It induces steroidogenic factor 1, which is instrumental in promoting Leydig cell differentiation (8, 9). It also promotes the deposition of basal lamina surrounding seminiferous tubules (6). Mutations of Dhh are linked to complete pure gonadal dysgenesis (10). Dhh is expressed in the female by ovarian granulosa cells and the corporus luteum (11). Its upregulation in ovarian cancer correlates positively with proliferative index, and negatively with prognosis (12). Dhh is also expressed by Schwann cells and is upregulated following nerve injury (13, 14). It induces the expression of Patched and Hip in neural tissue fibroblasts and promotes the formation of the connective tissue sheath surrounding peripheral nerves (13).