What does time mean in development?

Abstract

Biology is dynamic. Timescales range from frenetic sub-second ion fluxes and enzymatic reactions to the glacial millions of years of evolutionary change. Falling somewhere in the middle of this range are the processes we usually study in development: cell division and differentiation, gene expression, cell-cell signalling, and morphogenesis. But what sets the tempo and manages the order of developmental events? Are the order and tempo different between species? How is the sequence of multiple events coordinated? Here, we discuss the importance of time for developing embryos, highlighting the necessity for global as well as cell-autonomous control. New reagents and tools in imaging and genomic engineering, combined with in vitro culture, are beginning to offer fresh perspectives and molecular insight into the origin and mechanisms of developmental time.

Fig. 1.

Time plays an important role in development. (A) The order of marker gene expression in embryonic stem-cell derived cortical neurogenesis. Reelin and Tbr1 are subplate or Cajal-Retzius neuron markers; Tbr1 and Ctip2 are deep layer neuron markers; Cux1 and Satb2 are upper layer makers. Redrawn from Gaspard et al. (2008). (B) Regular oscillations in gene expression in the pre-somitic mesoderm correlate with the rhythmic generation of somites. Red and blue lines represent the levels of a Lfng reporter in two neighbouring regions of tissue in cultured pre-somitic mesoderm, indicating in-phase synchronization. Adapted from Tsiairis and Aulehla (2016), where it was published under a CC-BY license (https://creativecommons.org/licenses/by/4.0/). (C) Motoneuron differentiation involves a series of changes in gene expression. These are identical in mouse and human but take different amounts of time. Nanog is a pluripotent stem cell marker; Sox1 is a neural progenitor marker; Olig2 is a motoneuron progenitor marker; Isl1, Hb9 and ChAT are terminal motoneuron markers. Reproduced from Davis-Dusenbery et al. (2014). (D) Developmental checkpoints coordinate the progression of Drosophila larvae. Ecdysone acts systemically to trigger pupariation and metamorphosis. The production of ecdysone can be delayed for several days if imaginal discs are damaged or their growth abnormal. An insulin-like peptide, Dilp8, is secreted from immature imaginal discs to block ecdysone production.