Work

Cell size asymmetry regulates neural stem cell proliferation and lineage expansion in the Drosophila brain

Year: 2026

Type: article

Abstract: Asymmetrically dividing invertebrate and vertebrate stem cells can produce unequal sibling cell sizes but the function of cell size asymmetry (CSA) remains underexplored. Here, we use Drosophila neural stem cells (NSCs) to investigate how changes in CSA affect cell fate decisions and neurogenesis. Using live-cell imaging, NSC lineage analysis, and gene expression profiling, we find that altering CSA expands the NSC pool but restricts lineage expansion. Ordinary differential equation (ODE) models suggest two possible mechanisms: NSC volume sensitivity and NSC self-inhibition. Consistent with the volume-sensitivity model, the NSC growth regulator Imp and the G1-S cell-cycle regulator CycE are upregulated in NSCs with altered CSA. In addition, the differentiation factor Prospero is asymmetrically inherited in symmetrically dividing NSCs, suggesting a mechanism for NSC self-inhibition. Together, our results suggest that cell size and cell fate determinants regulate NSC proliferation lineage expansion and progeny differentiation in the developing Drosophila brain.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118248