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bioRxiv · 10.64898/2026.05.20.726652

Neural stem cells shape intracellular calcium landscapes to control cell identity and function

Lin, B. C.·Maag, I. R.·Shaw, H. M.·Jester, A. G.·Swan Adams, A. B.·Piggott, B. J.
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Abstract

Asymmetrically dividing neural stem cells (NSCs) provide the foundation for brain development by coupling self-renewal to the generation of diverse differentiated progeny. Yet how NSCs actively sculpt intracellular Ca{superscript 2} dynamics to drive developmental programs and cell behaviors across fate transitions remains poorly understood. Here we identify a role for intracellular Ca2+ set points in maintaining NSC identity and function in asymmetrically dividing Drosophila neuroblasts (NB). We find that proliferative NBs maintain low baseline cytosolic Ca2+, whereas differentiated progeny exhibit elevated cytosolic Ca2+. Experimentally increasing cytosolic Ca2+ slows proliferation and promotes differentiation. We further identify specific Ca2+ regulatory factors that are required for proliferation. Endoplasmic Reticulum (ER) luminal Ca2+ also differs by cell fate and depletion of ER Ca2+ in type II NB by loss of SERCA (Sarcoendoplasmic Reticulum ATPase) is sufficient to reprogram type II NB into a "type I-like" NB fate. Mechanistically, SERCA-dependent ER luminal Ca2+ is required for Notch receptor processing, trafficking and activation in NBs linking organellar Ca2+ to a core stem cell signaling pathway. Thus, NSCs and their progeny actively and distinctly shape intracellular Ca2+ landscapes to drive developmental programs and cell behaviors, with implications for developmental disorders and cancer.

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Lin, B. C., Maag, I. R., Shaw, H. M., Jester, A. G., Swan Adams, A. B., Piggott, B. J.. 2026-05-21. Neural stem cells shape intracellular calcium landscapes to control cell identity and function. https://doi.org/10.64898/2026.05.20.726652

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