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 how it contributes to tissue morphogenesis are not fully understood. In this study, we show that intracellular calcium ions (Ca 2+ ) are required for Xenopus neural tube formation and that there are two types of Ca 2+ -concentration changes, a single-cell and a multicellular wave-like fluctuation, in the developing neural plate. Quantitative imaging analyses revealed that transient increases in Ca 2+ 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 (cdh2) participate in the Ca 2+ -induced apical constriction. Furthermore, our mathematical model suggests that the effect of Ca 2+ fluctuations on tissue morphogenesis is independent of fluctuation frequency and that fluctuations affecting individual cells are more efficient than those at the multicellular level. We propose that distinct Ca 2+ signaling patterns differentially modulate apical constriction for efficient epithelial folding and that this mechanism has a broad range of physiological outcomes.

In vivo optochemical control of cell contractility at single‐cell resolution

“…The detailed mechanism of how Ca 2+ is functionally linked to contractile actomyosin also remains unclear, although there is no doubt that Ca 2+ is involved in regulation of contractility in many cell types [10][11][12][13][14]16]. It is clear that Ca 2+ does not directly act on actomyosin similar to the contractile system involving troponin C, given the time lag between Ca 2+ burst and contractility in the range of many seconds.…”

The Secretory Pathway Calcium ATPase 1 (SPCA1) controls neural tube closure by regulating cytoskeletal dynamics

“…Although these studies reveal that intracellular calcium levels are crucial for neural tube closure, a direct link between calcium and apical constriction during neurulation has only recently been uncovered by two recent studies using live imaging of frog embryos. These studies revealed that apical constriction during neurulation involves cellautonomous and asynchronous pulsed apical contractions that are preceded by flashes of calcium (Christodoulou and Skourides, 2015;Suzuki et al, 2017). These calcium pulses also correlate with accumulation of F-actin in the medial region of neuroepithelial cells, suggesting that calcium regulates apical constriction by influencing actin dynamics and/or myosin contractility.…”

Hingepoints and neural folds reveal conserved features of primary neurulation in the zebrafish forebrain

“…Assembly of this actomyosin network occurs via oscillatory constrictions with gradually decreasing amplitude, akin to the ratchet model initially proposed in invertebrates [50][51][52] and later reported during neural tube closure in Xenopus 53 . We further show that disruption of myosin impairs NF convergence, possibly by contributing a "pulling force" on the NFs or by clearing the dorsal midline of eye field cells.…”