Biology subjects

Piggott, B. J.

Publications and source records attributed to Piggott, B. J..

2 recordsLinked to original sources

bioRxiv2026

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

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.

developmental biology↗

bioRxiv2019

Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors

Proliferating cells, typically considered \"non-excitable,\" nevertheless exhibit regulation by bioelectrical signals. Notably, voltage-gated sodium channels (VGSC) that are crucial for neuronal excitability, are also found in progenitors and upregulated in cancer. Here, we identify a role for VGSC in proliferation of Drosophila neuroblast (NB) lineages within the central nervous system. Loss of paralytic (para), the sole gene that encodes Drosophila VGSC, reduces neuroblast progeny cell number. The type II neuroblast lineages, featuring a transit-amplifying intermediate neural progenitors (INP) population similar to that found in the developing human cortex, are particularly sensitive to para manipulation. Following a series of asymmetric divisions, INPs normally exit the cell cycle through a final symmetric division. Our data suggests that loss of para induces apoptosis in this population, whereas overexpression leads to an increase in INPs and overall neuroblast progeny cell numbers. These effects are cell autonomous and depend on Para channel activity. Reduction of Para not only affects normal NB development, but also strongly suppresses brain tumor mass, implicating a role for Para in cancer progression. To our knowledge, our studies are the first to identify a role for VGSC in neural progenitor proliferation. Elucidating the contribution of VGSC in proliferation will advance our understanding of bioelectric signaling within development and disease states.

developmental biology↗