The T-type Ca2+ Channel Cav3.2 Regulates Differentiation of Neural Progenitor Cells during Cortical Development via Caspase-3. (15th March 2019)

• Record Type: Journal Article
• Authors: Rebellato, Paola; Kaczynska, Dagmara; Kanatani, Shigeaki; Rayyes, Ibrahim Al; Zhang, Songbai; Villaescusa, Carlos; Falk, Anna; Arenas, Ernest; Hermanson, Ola; Louhivuori, Lauri; Uhlén, Per
• Is Part Of: Neuroscience. Volume 402(2019)
• Page Start: 78
• Page End: 89
• Publication Date: 2019-03-15
• Subjects: spontaneous Ca2+ activity -- Cacna1h -- neural differentiation -- caspase-3 -- T-type calcium channels; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.01.015
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Spontaneous Ca 2+ activity in NPCs is regulated by the Cav 3.2 gene Cacna1h . Ca 2+ active NPCs have enhanced caspase-3 activity, unrelated to apoptosis. Cav 3.2 inhibition decreases caspase-3 activity and suppresses NPC differentiation. Cacna1h KO embryonic brains display attenuated spontaneous Ca 2+ activity. Cacna1h KO embryonic brains show impaired neocortical layer formation. Abstract: Here we report that the low-voltage-dependent T-type calcium (Ca 2+ ) channel Cav 3.2, 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 Ca 2+ activity. This activity strongly correlated with the upregulation of CACNA1H mRNA. Cells exhibiting robust spontaneous Ca 2+ signaling had increased caspase-3 activity unrelated to apoptosis. Inhibition of Cav 3.2 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 Ca 2+ 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 Cav 3.2 and caspase-3 signaling that affects neurogenesis in the developing brain.