Abstract:

Early radial glia (RG) choose their fate in the subpallium to produce intermediate neural progenitor or somatostatin-expressing interneuron. The neurotransmitter γ-aminobutyric acid (GABA) serves as one of the earliest neurotransmitters and exerts excitatory effects crucial for VZ progenitor proliferation through Ca²⁺ signals. However, the Ca²⁺ regulatory mechanisms remain unknown, especially in the early ventral forebrain. Our study identifies GABA signal induces Orai1-dependent store-operated-Ca²⁺ entry (SOCE) in the ventral RG (vRG). In particular, a novel subpopulation of Anoctamin 1 (ANO1/TMEM16a)-expressing vRGs that utilizes ANO1 to modulate GABA-dependent SOCE is essential for generating SST⁺ interneurons. These findings elucidate new aspects of Ca²⁺ regulatory mechanisms in early vRGs during neural development, highlighting the potential impact of pharmacological modulators of ANO1 and GABA_A receptors on RG cell fate during early pregnancy.