UCSF

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 ofDrosophilaneuroblast (NB) lineages within the central nervous system. Loss ofparalytic (para), the sole gene that encodesDrosophilaVGSC, 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 toparamanipulation. Following a series of asymmetric divisions, INPs normally exit the cell cycle through a final symmetric division. Our data suggests that loss ofparainduces 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.