The Hedgehog receptor Boi limits stem cell proliferation by retaining Hedgehog (Hh) at its source, Hartman et al. report.

In Drosophila ovaries, Hh stimulates follicle stem cells (FSCs) to proliferate and form the outer epithelial layer of developing egg chambers. Hh ligand is secreted by apical cells at the anterior end of ovaries, several cell lengths away from FSCs, which express the Hh receptor Patched and downstream components of the signaling pathway such as Smoothened and the transcription factor Ci.

Boi is a coreceptor for Hh, but Hartman et al. found that this protein was expressed on the surface of apical cells rather than on FSCs. Moreover, FSC proliferation increased when Boi was mutated or depleted from apical cells, indicating that the receptor suppresses Hh signaling in Drosophila ovaries. In the absence of Boi, apical cells failed to sequester Hh after secreting it, leading to increased amounts of the ligand reaching FSCs. FSC hyperproliferation was reversed by reducing Hh levels or by depleting Smoothened and Ci from the stem cells. Apical cells don't express these downstream effectors, the researchers found, preventing them from being activated when Boi binds Hh.

Senior author Alana O'Reilly now wants to investigate why apical cells limit the signal they send to FSCs by sequestering Hh rather than by decreasing expression of the protein. One possibility is that it enables ovaries to increase FSC proliferation and egg production rapidly in response to environmental changes, allowing flies to lay eggs only when conditions are favorable.

et al
J. Cell Biol.