Control of the number of cell division rounds in distinct tissues during ascidian embryogenesis

An important question in developmental biology is how the number of cells constituting the body is regulated during development. After termination of cell divisions, cells enter the postmitotic phase, but the mechanisms determining the timing of final cell division remain unclear. In ascidians, the egg develops into a tadpole larva consisting of a relatively small number of cells (approximately 2800), indicating that embryonic cells divide 11.5 times on average after fertilization, although the number of cell division rounds differs among tissues. This article discusses the possible mechanisms that control the timing of the final cell division: these include (i) the analog and digital clock models, in which the elapsed time and number of cell division cycles are measured after fertilization, respectively, and (ii) the analog and digital timer models, in which the elapsed time and number of cell divisions are measured after cell fate specification, respectively. In notochord and muscle cells of ascidian embryos, cell division termination involves cell fate specification by inductive FGF signaling, followed by activation of the tissue-specific key transcription factors, Brachyury and Tbx6, which then induce gene expression of an effector, Cdk inhibitor. The present evidence suggests that these timing mechanisms comprise two functional phases: (i) an analog timer, which is mediated by accumulation of Cdk inhibitor protein after cell fate specification, and (ii) a timekeeper, which confines the timing, when the above timer is triggered by Brachyury and Tbx6, to the appropriate stage.