Intracellular calcium (Ca2+) signaling is a central regulator of corticogenesis, governing haveneural stem cell behavior, fate transitions, neuronal migration, and circuit assembly. Beyond its canonical role as a second messenger, Ca2+ shapes cytoskeletal organization by modulating microtubule dynamics essential for mitotic spindle function, radial glial scaffold, nucleokinesis, and neurite extension. This review synthesizes evidence from in vivo, ex vivo, and in vitro studies to delineate Ca2+-dependent pathways and Ca2+-binding proteins that couple, within restricted Ca2+ microdomains in space and time, to microtubule regulation during mammalian cortical development. We highlight mechanistic nodes involving calmodulin, Ca2+/calmodulin-dependent kinases (CaMKs), S100 proteins, cadherins/protocadherins, centrins (CENs), and Ca2+ sensors such as STIM1 and calneurons, which collectively coordinate spindle orientation, progenitor division modes, radial migration, and neurite outgrowth. Finally, we discuss how perturbations in Ca2+-controlled cytoskeletal programs may contribute to abnormal cortical cytoarchitecture and neurodevelopmental disease. By integrating Ca2+ microdomain transients with microtubule control modules, this review provides a unified framework for understanding how Ca2+ orchestrates key cellular events during mammalian corticogenesis and propose that Ca2+ oscillatory codes are translated into direct or indirect microtubule/cytoskeletal remodeling transitions that determine neural stem cell fate, migration, and maturation, to accurately establish cortical architecture and function.
Merced-García et al. (Fri,) studied this question.