Microproteins Simba1 and Simba2 activate Wingless signaling during the reactivation of neural stem cells in Drosophila.

ABSTRACT: The ability of neural stem cells (NSCs) to switch between quiescent and proliferative states is fundamental for adult neurogenesis and regeneration. Microproteins or short open reading frame (sORF)-encoded peptides (SEPs), are highly abundant yet largely understudied, and their role in brain development remains unclear. Here, we demonstrate that two evolutionarily-conserved microprotein paralogs, Simba1 and Simba2, encoded by sORFs CG15715 and CG18081, respectively, govern the reactivation of Drosophila quiescent NSCs. Both Simba1 and Simba2 function in NSCs and Blood-Brain-Barrier (BBB) glial cells to promote NSC reactivation. Mechanistically, Simba1 and Simba2 act as transcription factors activating the WNT/Wingless signalling pathway during NSC reactivation. We uncover a critical role o

SUBMITTER: Lin J 

PROVIDER: S-EPMC12749969 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature