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

Investigating the mechanisms that maintain different types of neural stem cells is essential for brain development. While factors maintaining distinct <i>Drosophila melanogaster</i> neuroblasts (NBs) have been identified, additional factors remain unidentified. In this paper, we find knockdown of <i>split ends</i> (<i>spen</i>) increases in nuclear Notch intracellular domain (NICD) level, which in turn activates Notch signaling in type II NBs. This activation causes the intermediate neural progenitors (imINPs) to dedifferentiate into type II NBs, thereby increasing the number of type II NBs specifically. Additionally, we find that knockdown of both <i>spen</i> and a co-repressor of the Notch signaling pathway, Hairless, in type II NBs exacerbates the increase in type II NBs number, compared to <i>spen</i> knockdown alone. Furthermore, we observe that loss of Spen results in more severe phenotypes than loss of 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.