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The T-type Ca2+ Channel Cav3.2 Regulates Differentiation of Neural Progenitor Cells during Cortical Development via Caspase-3

Rebellato, Paola ; Kaczynska, Dagmara ; Kanatani, Shigeaki ; Rayyes, Ibrahim Al ; Zhang, Songbai ; Villaescusa, Carlos ; Falk, Anna LU ; Arenas, Ernest ; Hermanson, Ola and Louhivuori, Lauri , et al. (2019) In Neuroscience 402. p.78-89
Abstract

Here we report that the low-voltage-dependent T-type calcium (Ca2+) channel Cav3.2, encoded by the CACNA1H gene, regulates neuronal differentiation during early embryonic brain development through activating caspase-3. At the onset of neuronal differentiation, neural progenitor cells exhibited spontaneous Ca2+ activity. This activity strongly correlated with the upregulation of CACNA1H mRNA. Cells exhibiting robust spontaneous Ca2+ signaling had increased caspase-3 activity unrelated to apoptosis. Inhibition of Cav3.2 by drugs or viral CACNA1H knock down resulted in decreased caspase-3 activity followed by suppressed neurogenesis. In contrast, when CACNA1H was overexpressed, increased neurogenesis was detected. Cortical slices from... (More)

Here we report that the low-voltage-dependent T-type calcium (Ca2+) channel Cav3.2, encoded by the CACNA1H gene, regulates neuronal differentiation during early embryonic brain development through activating caspase-3. At the onset of neuronal differentiation, neural progenitor cells exhibited spontaneous Ca2+ activity. This activity strongly correlated with the upregulation of CACNA1H mRNA. Cells exhibiting robust spontaneous Ca2+ signaling had increased caspase-3 activity unrelated to apoptosis. Inhibition of Cav3.2 by drugs or viral CACNA1H knock down resulted in decreased caspase-3 activity followed by suppressed neurogenesis. In contrast, when CACNA1H was overexpressed, increased neurogenesis was detected. Cortical slices from Cacna1h knockout mice showed decreased spontaneous Ca2+ activity, a significantly lower protein level of cleaved caspase-3, and microanatomical abnormalities in the subventricular/ventricular and cortical plate zones when compared to their respective embryonic controls. In summary, we demonstrate a novel relationship between Cav3.2 and caspase-3 signaling that affects neurogenesis in the developing brain.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Calcium Channels, T-Type/genetics, Calcium Signaling, Caspase 3/metabolism, Cell Differentiation, Cerebral Cortex/growth & development, Gene Expression Regulation, Developmental, Lateral Ventricles/metabolism, Mice, Inbred C57BL, Mice, Knockout, Neural Stem Cells/metabolism, Neuroepithelial Cells/metabolism
in
Neuroscience
volume
402
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:85061132015
  • pmid:30677486
ISSN
1873-7544
DOI
10.1016/j.neuroscience.2019.01.015
language
English
LU publication?
no
id
df7448c3-664f-442f-8b4d-affddbd98a75
date added to LUP
2021-08-09 15:53:34
date last changed
2024-05-04 10:03:09
@article{df7448c3-664f-442f-8b4d-affddbd98a75,
  abstract     = {{<p>Here we report that the low-voltage-dependent T-type calcium (Ca2+) channel Cav3.2, encoded by the CACNA1H gene, regulates neuronal differentiation during early embryonic brain development through activating caspase-3. At the onset of neuronal differentiation, neural progenitor cells exhibited spontaneous Ca2+ activity. This activity strongly correlated with the upregulation of CACNA1H mRNA. Cells exhibiting robust spontaneous Ca2+ signaling had increased caspase-3 activity unrelated to apoptosis. Inhibition of Cav3.2 by drugs or viral CACNA1H knock down resulted in decreased caspase-3 activity followed by suppressed neurogenesis. In contrast, when CACNA1H was overexpressed, increased neurogenesis was detected. Cortical slices from Cacna1h knockout mice showed decreased spontaneous Ca2+ activity, a significantly lower protein level of cleaved caspase-3, and microanatomical abnormalities in the subventricular/ventricular and cortical plate zones when compared to their respective embryonic controls. In summary, we demonstrate a novel relationship between Cav3.2 and caspase-3 signaling that affects neurogenesis in the developing brain.</p>}},
  author       = {{Rebellato, Paola and Kaczynska, Dagmara and Kanatani, Shigeaki and Rayyes, Ibrahim Al and Zhang, Songbai and Villaescusa, Carlos and Falk, Anna and Arenas, Ernest and Hermanson, Ola and Louhivuori, Lauri and Uhlén, Per}},
  issn         = {{1873-7544}},
  keywords     = {{Animals; Calcium Channels, T-Type/genetics; Calcium Signaling; Caspase 3/metabolism; Cell Differentiation; Cerebral Cortex/growth & development; Gene Expression Regulation, Developmental; Lateral Ventricles/metabolism; Mice, Inbred C57BL; Mice, Knockout; Neural Stem Cells/metabolism; Neuroepithelial Cells/metabolism}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{78--89}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience}},
  title        = {{The T-type Ca2+ Channel Cav3.2 Regulates Differentiation of Neural Progenitor Cells during Cortical Development via Caspase-3}},
  url          = {{https://lup.lub.lu.se/search/files/101035970/The_T_type_Ca2_Channel.pdf}},
  doi          = {{10.1016/j.neuroscience.2019.01.015}},
  volume       = {{402}},
  year         = {{2019}},
}