Proper control of stem cell behavior is crucial for maintaining tissue homeostasis. In the Drosophila midgut, smooth septate junction (sSJ)-associated proteins play a crucial role in regulating intestinal stem cell (ISC) proliferation via atypical PKC (aPKC) activity. Here, we investigate the underlying mechanism. We found that aPKC in the apical cortex diminishes during enteroblast differentiation, in accordance with the apical accumulation of sSJ proteins. In sSJ protein-deficient conditions, aPKC remained in the apical cortex in enteroblasts, accompanied by ISC overproliferation. Manipulation of Kibra, an activator of the Hippo pathway with aPKC-binding properties, affected sSJ proteins depletion-induced ISC overproliferation in an aPKC-binding domain-dependent manner, revealing a link between aPKC and the Hippo- and/or Misshapen-Yorkie pathway in ISC proliferation. This study provides novel insights into the mechanism underlying stem cell regulation, in which an antagonistic interaction between aPKC and junctional proteins in differentiating progenitors is involved.
Izumi et al. (2026) studied this question.