Boi keeps Hedgehog close to home

Boi keeps Hedgehog close to home T he Hedgehog receptor Boi limits stem cell proliferation by retaining Hedgehog (Hh) at its source, Hartman et al. report. In Drosophila ovaries , Hh stimulates fol-licle stem cells (FSCs) to proliferate and form the outer epithelial layer of developing egg chambers. Hh ligand is secreted by api-cal 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 fl ies to lay eggs only when conditions are favorable. E RK MAP kinases disrupt the interaction between lamin A and the retinoblastoma (Rb) protein to drive cell proliferation , Rodríguez et al. report. In response to growth factors, active ERKs enter the nucleus and stimulate cell cycle entry and progression by several different mechanisms. One of ERK's earliest actions is to bind lamin A at the nuclear periphery, where it phosphorylates and releases the transcription factor c-Fos. Rodríguez et al. noticed that the ERK-binding site on lamin A overlapped with the binding site for the Rb tumor suppressor, which inhibits cell cycle entry by sequestering the E2F family of transcription factors. Both ERK1 and ERK2 competed with Rb for binding to lamin A, the team found, and displaced the tumor suppressor into the nucleoplasm, where it was phosphorylated and inactivated. ERKs lacking kinase activity could also dislodge and switch off Rb if …