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

Publication date: Available online 21 January 2019Source: NeuroscienceAuthor(s): Paola Rebellato, Dagmara Kaczynska, Shigeaki Kanatani, Ibrahim Al Rayyes, Songbai Zhang, Carlos Villaescusa, Anna Falk, Ernest Arenas, Ola Hermanson, Lauri Louhivuori, Per UhlénAbstractHere 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 over-expressed, 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.

Source: Neuroscience - January 21, 2019 Category: Neuroscience Source Type: research