Distinct intracellular Ca2+ dynamics regulate apical constriction and differentially contribute to neural tube closure

Abstract

Early in the development of the central nervous system, progenitor cells undergo a shape change, called apical constriction, that triggers the neural plate to form a tubular structure. How apical constriction in the neural plate is controlled, and contributes to tissue morphogenesis, are not fully understood. In this study, we show that intracellular calcium ions (Ca2+) are required for Xenopus neural tube formation, and that there are two types of Ca2+-concentration changes, a single-cell and a multicellular wave-like fluctuation, in the developing neural plate. Quantitative imaging analyses revealed that transient increases in Ca2+ concentration induced cortical F-actin remodeling, apical constriction, and accelerations of the closing movement of the neural plate. We also show that extracellular ATP and N-cadherin participate in the Ca2+-induced apical constriction. Furthermore, our mathematical model suggests that the effect of Ca2+ fluctuations on tissue morphogenesis was independent of its frequency, and fluctuations affecting individual cells were more efficient than those at the multicellular level. We propose that distinct Ca2+ signaling patterns differentially modulate apical constriction for efficient epithelial folding and this mechanism has broad physiological outcomes.