Type-1 astrocyte-like stem cells harboring Cacna1d gene deletion exhibit reduced proliferation and decreased neuronal fate choice.
In the central nervous system, CaV 1.2 and CaV 1. 3 constitute the main L-type voltage-gated calcium channels (LTCCs) coupling membrane depolarization to gene transcription. We have previously demonstrated that inducible disruption of Cav1.2 in type-1 astrocyte-like stem cells of the adult dentate gyrus (DG) impairs hippocampal neurogenesis in a cell-autonomous fashion. To address the role of Cav1.3 channels (encoded by the Cacna1d gene), we here generated TgGLAST-CreERT2 /Cacna1dfl/fl /RCE:loxP mice which facilitate inducible deletion of Cacna1d in tandem with induction of EGFP expression in type-1 cells, allowing tracking of recombined cells and their descendants. Neurosphere cultures derived from fluorescence-activated cell sorting sorted Cacna1d-deficient (Cacna1d-/- /EGFP) hippocampal neural precursor cells (NPCs) exhibited a significant decrease in proliferative activity. Further, under differentiation conditions, Cacna1d deficiency conferred an increase in astrogenesis at the expense of neurogenesis. In like manner, type-1 cells lacking Cacna1d showed reduced proliferation in the dentate gyrus (DG) in vivo. Moreover, Cacna1d deficiency resulted in a significant decrease in the number of newly born cells adopting a neuronal fate. Finally, massive excitation induced by repeated electroconvulsive seizures rescued the proliferation defect of Cacna1d-/- /EGFP type-1 cells. Together, the effects of Cacna1d gene deletion closely recapitulate our earlier findings on the role of Cav1.2 channels expressed by type-1 cells. Similar to Cav1.2 channels, Cav1.3 channels on type-1 cells boost type-1 cell proliferation and promote subsequent neuronal fate choice.
['Völkening|Bianca|B|0000-0002-6616-1574', 'Schönig|Kai|K|', 'Kronenberg|Golo|G|', 'Bartsch|Dusan|D|', 'Weber|Tillmann|T|']
D000818:Animals D020746:Calcium Channels, L-Type D002454:Cell Differentiation D049109:Cell Proliferation D002478:Cells, Cultured D018891:Dentate Gyrus D000089622:Doublecortin Domain Proteins D004558:Electric Stimulation D004827:Epilepsy D027341:Excitatory Amino Acid Transporter 1 D005260:Female D017353:Gene Deletion D049452:Green Fluorescent Proteins D019394:Ki-67 Antigen D008297:Male D051379:Mice D008822:Mice, Transgenic D008869:Microtubule-Associated Proteins D058953:Neural Stem Cells D055495:Neurogenesis D009474:Neurons D009479:Neuropeptides
Cacna1d Cav1.3 L-type voltage gated calcium channel adult hippocampal neurogenesis neural stem cell