Split ends Inhibits the Dedifferentiation of imINP to Prevent the Generation of Supernumerary Type II Neuroblasts in Drosophila

Investigating the mechanisms maintaining different types of neural stem cells is essential for brain development. While factors maintaining distinct Drosophila neuroblasts (NBs) have been identified, additional factors remain unidentified. In this paper, we find knockdown of split ends (spen) enhances the activity of Notch signaling in type II NBs, and then leading to the intermediate neural progenitors (imINPs) dedifferentiate into type II NBs, thereby increasing type II NBs number specifically. Additionally, we find that knockdown of both spen and a co-repressor of the Notch signaling pathway-Hairless in type II NBs exacerbates the increase in type II NBs number, compared to spen knockdown alone. Furthermore, we observe that spen seems to play a more critical role than Hairless in type II NBs and their lineages. We reveal that SPEN may indeed function as a functional homolog of its mammalian homolog-SHARP, acting as a novel Notch signaling co-repressor in type II NBs specifically. This highlights the potential for multiple co-repressors to collaboratively regulate the same signaling pathway within the type II NBs lineage. The distinct regulatory mechanism of type I and II NBs offers new insights into the study of neural stem cell homeostasis.