Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind

AUTOR(ES)

Vied, Cynthia

FONTE

Company of Biologists

RESUMO

Normal self-renewal of follicle stem cells (FSCs) in the Drosophila ovary requires Hedgehog (Hh) signaling. Excess Hh signaling, induced by loss of patched (ptc), causes cell-autonomous duplication of FSCs. We have used a genetic screen to identify Mastermind (Mam), the Notch pathway transcriptional co-activator, as a rare dose-dependent modifier of aberrant FSC expansion induced by excess Hh. Complete loss of Mam activity severely compromises the persistence of both normal and ptc mutant FSCs, but does not affect the maintenance of ovarian germline stem cells. Thus, Mam, like Hh, is a crucial stem cell factor that acts selectively on FSCs in the ovary. Surprisingly, other Notch pathway components, including Notch itself, are not similarly required for FSC maintenance. Furthermore, excess Notch pathway activity alone accelerates FSC loss and cannot ameliorate the more severe defects of mam mutant FSCs. This suggests an unconventional role for Mam in FSCs that is independent of Notch signaling. Loss of Mam reduces the expression of a Hh pathway reporter in FSCs but not in wing discs, suggesting that Mam might enhance Hh signaling specifically in stem cells of the Drosophila ovary.

Documentos Relacionados

• Non-canonical inteins.
• SpliceDB: database of canonical and non-canonical mammalian splice sites
• Analysis of canonical and non-canonical splice sites in mammalian genomes
• Ubiquitylation on Canonical and Non-canonical Sites Targets the Transcription Factor Neurogenin for Ubiquitin-mediated Proteolysis*
• The CBP co-activator stimulates E2F1/DP1 activity.