Termination of Notch signaling is essential for the specification of differentiating progeny during asymmetric stem cell division. Using Drosophila type II neural stem cells as a model, here we report that, in addition to asymmetric segregation of Numb, fate specification of differentiating progeny also requires the expression of the Notch target E(Spl)mγ in the stem cell to be kept at low levels by the SPEN family proteins, Split End (Spen) and Spenito (Nito). Loss of Spen or Nito leads to a drastic increase in E(Spl)mγ expression in the stem cell and dedifferentiation of the progeny. We demonstrate that Spen and Nito repress E(Spl)mγ expression by binding to two identical motifs in the 5' untranslated region to repress the translation. The low E(Spl)mγ expression in the stem cell ensures its rapid removal from the progeny. Together, our work uncovers a post-transcriptional mechanism regulating Notch signaling during asymmetric stem cell division.
Li et al. (Wed,) studied this question.