Gene transcription is coordinated with, but not dependent on, cell divisions during C. elegans embryonic fate specification

Cell differentiation and proliferation are coordinated during animal development, but the link between them remains uncharacterized. To examine this relationship, we combined single-molecule RNA imaging with time-lapse microscopy to generate high-resolution measurements of transcriptional dynamics in Caenorhabditis elegans embryogenesis. We found that globally slowing the overall development rate of the embryo by altering temperature or by mutation resulted in cell proliferation and transcription slowing, but maintaining, their relative timings, suggesting that cell division may directly control transcription. However, using mutants with specific defects in cell cycle pathways that lead to abnormal lineages, we found that the order between cell divisions and expression onset can switch, showing that expression of developmental regulators is not strictly dependent on cell division. Delaying cell divisions resulted in only slight changes in absolute expression time, suggesting that expression and proliferation are independently entrained to a separate clock-like process. These changes in relative timing can change the number of cells expressing a gene at a given time, suggesting that timing may help determine which cells adopt particular transcriptional patterns. Our results place limits on the types of mechanisms that are used during normal development to ensure that division timing and fate specification occur at appropriate times.