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Genes Dev. 2019 Dec 1;33(23-24):1739-1750. doi: 10.1101/gad.330597.119. Epub 2019 Nov 21.

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

Author information

1
Department of Physiology, Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA.
2
Howard Hughes Medical Institute.
3
Neuroscience Initiative, Advanced Science Research Center, the Graduate Center, City University of New York, New York 10031, New York.
4
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
5
Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
6
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 3E1, Canada.

Abstract

Proliferating cells, typically considered "nonexcitable," nevertheless, exhibit regulation by bioelectric signals. Notably, voltage-gated sodium channels (VGSC) that are crucial for neuronal excitability are also found in progenitors and up-regulated 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 population of transit-amplifying intermediate neural progenitors (INP) 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 expression 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.

KEYWORDS:

cancer biology; development; drosophila; neuroscience; proliferation; stem cells

PMID:
31753914
PMCID:
PMC6942049
[Available on 2020-06-01]
DOI:
10.1101/gad.330597.119
[Indexed for MEDLINE]

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