The RNA-binding protein Modulo promotes neural stem cell maintenance in Drosophila

PLoS One. 2024 Dec 19;19(12):e0309221. doi: 10.1371/journal.pone.0309221. eCollection 2024.

Abstract

A small population of stem cells in the developing Drosophila central nervous system generates the large number of different cell types that make up the adult brain. To achieve this, these neural stem cells (neuroblasts, NBs) divide asymmetrically to produce non-identical daughter cells. The balance between stem cell self-renewal and neural differentiation is regulated by various cellular machinery, including transcription factors, chromatin remodelers, and RNA-binding proteins. The list of these components remains incomplete, and the mechanisms regulating their function are not fully understood, however. Here, we identify a role for the RNA-binding protein Modulo (Mod; nucleolin in humans) in NB maintenance. We employ transcriptomic analyses to identify RNA targets of Mod and assess changes in global gene expression following its knockdown, results of which suggest a link with notable proneural genes and those essential for neurogenesis. Mod is expressed in larval brains and its loss leads to a significant decrease in the number of central brain NBs. Stem cells that remain lack expression of key NB identity factors and exhibit cell proliferation defects. Mechanistically, our analysis suggests these deficiencies arise at least in part from altered cell cycle progression, with a proportion of NBs arresting prior to mitosis. Overall, our data show that Mod function is essential for neural stem cell maintenance during neurogenesis.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental
  • Larva / genetics
  • Larva / metabolism
  • Neural Stem Cells* / cytology
  • Neural Stem Cells* / metabolism
  • Neurogenesis
  • Nucleolin
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • RNA-Binding Proteins
  • Drosophila Proteins
  • Nucleolin
  • Phosphoproteins

Grants and funding

Research reported in this publication was supported by the National Science Foundation (https://www.nsf.gov) under award numbers 2205405 (C.A.J) and 1628471 (A.S.P), the National Institutes of Health (https://www.nih.gov) under award number R01-GM108756 (C.A.J), and the Department of Energy (https://www.energy.gov) and Office of the Director of National Intelligence (https://www.dni.gov) under the award number ICPD-2022-14 (A.S.P). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Science Foundation, National Institutes of Health, or the Department of Energy and Office of the Department of National Intelligence. There was no additional external funding received for this study.