Spen and Nito prevent dedifferentiation of intermediate progenitors by maintaining Notch target expression in stem cells at low levels.

Xiaosu Li, Wenwen Lu, Marisa Connell, Xiaobing Deng, Rui Chen, Sijun Zhu

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Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Xiaosu LiDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

Wenwen LuDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

Marisa ConnellDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

Xiaobing DengDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

Rui ChenDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

Sijun ZhuDepartment of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA. Electronic address: zhus@upstate.edu.

Funding

Generation of Intermediate Neural Progenitors in Drosophila Larval BrainsR01NS085232 · NINDS · UPSTATE MEDICAL UNIVERSITY · PI ZHU, SIJUN · 2014 to 2024

$3.5M

NINDS NIH HHS R01 NS085232

6 · The paper itself

Abstract

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.

Indexed as

5′ untranslated regionasymmetric divisionCP: stem cell researchDrosophilaE(Spl)mγintermediate progenitorneuroblastsNitoNotchSpentranslation

Identifiers

PMID41886453

DOI10.1016/j.celrep.2026.117194

PMCPMC13188935

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.