Fig. 7.

Proposed model of cholesterol-free and cholesterol-bound Hh secretion in Drosophila: Cholesterol-bound and free forms of Hh are both secreted and have distinct and synergic functions. 1. Hh-producing cells synthesize lipid-anchored Hh protein. 2. Processed Hh protein can be secreted as an Lpp-bound form. An unknown esterase mechanism removes cholesterol and generates a cholesterol-free pool of Hh. 3. Cholesterol-free Hh can be secreted without Lpp. 4. Lpp-associated Hh stabilizes inactive full-length Ci-155. 5. Lpp-free Hh reduces the amount of cleaved Ci-75. 6. Lpp-free Hh also promotes the conversion of inactive Ci-155 into active full-length Ci-155. 7. Lpp-free Hh functions in synergy with Lpp-associated Hh to ultimately activate Hh target gene expression