title: Gene transcription is coordinated with, but not dependent on, cell divisions during C. elegans embryonic fate specification.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321, USA.
authors.forename: Gautham
authors.initials: G
authors.lastname: Nair
authors.forename: Travis
authors.initials: T
authors.lastname: Walton
authors.forename: John Isaac
authors.initials: JI
authors.lastname: Murray
authors.forename: Arjun
authors.initials: A
authors.lastname: Raj
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D047108:Embryonic Development; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057850:Hermaphroditic Organisms; D026161:MADS Domain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C094134:ELT-2 protein, C elegans; D050980:GATA Transcription Factors; D026161:MADS Domain Proteins; C516540:UNC-120 protein, C elegans
keywords: Cell division; Gene expression; RNA FISH; Time-lapse; Timing; Transcription