Coordination of mitosis and morphogenesis: role of a prolonged G2 phase during chordate neurulation

Chordates undergo a characteristic morphogenetic process during neurulation to form a dorsal hollow neural tube. Neurulation begins with the formation of the neural plate and ends when the left epidermis and right epidermis overlying the neural tube fuse to close the neural fold. During these processes, mitosis and the various morphogenetic movements need to be coordinated. In this study, we investigated the epidermal cell cycle in Ciona intestinalis embryos in vivo using a fluorescent ubiquitination-based cell cycle indicator (Fucci). Epidermal cells of Ciona undergo 11 divisions as the embryos progress from fertilization to the tadpole larval stage. We detected a long G2 phase between the tenth and eleventh cell divisions, during which fusion of the left and right epidermis occurred. Characteristic cell shape change and actin filament regulation were observed during the G2 phase. CDC25 is probably a key regulator of the cell cycle progression of epidermal cells. Artificially shortening this G2 phase by overexpressing CDC25 caused precocious cell division before or during neural tube closure, thereby disrupting the characteristic morphogenetic movement. Delaying the precocious cell division by prolonging the S phase with aphidicolin ameliorated the effects of CDC25. These results suggest that the long interphase during the eleventh epidermal cell cycle is required for neurulation.