title: A quantitative model of normal Caenorhabditis elegans embryogenesis and its disruption after stress.
abstract: The invariant lineage of Caenorhabditis elegans has powerful potential for quantifying developmental variability in normal and stressed embryos. Previous studies of division timing by automated lineage tracing suggested that variability in cell cycle timing is low in younger embryos, but manual lineage tracing of specific lineages suggested that variability may increase for later divisions. We developed improved automated lineage tracing methods that allowroutine lineage tracing through the last round of embryonic cell divisions and we applied these methods to trace the lineage of 18 wild-type embryos. Cell cycle lengths, division axes and cell positions are remarkably consistent among these embryos at all stages, with only slight increase in variability later in development. The resulting quantitative 4-dimensional model of embryogenesis provides a powerful reference dataset to identify defects in mutants or in embryos that have experienced environmental perturbations. We also traced the lineages of embryos imaged at higher temperatures to quantify the decay in developmental robustness under temperature stress. Developmental variability increases modestly at 25°C compared with 22°C and dramatically at 26°C, and we identify homeotic transformations in a subset of embryos grown at 26°C. The deep lineage tracing methods provide a powerful tool for analysis of normal development, gene expression and mutants and we provide a graphical user interface to allow other researchers to explore the average behavior of arbitrary cells in a reference embryo.
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA. julia.l.richards@gmail.com
authors.forename: Julia L
authors.initials: JL
authors.lastname: Richards
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Zacharias
authors.forename: Travis
authors.initials: T
authors.lastname: Walton
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Burdick
authors.forename: John Isaac
authors.initials: JI
authors.lastname: Murray
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005821:Genetic Techniques; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D012984:Software; D013312:Stress, Physiological; D013696:Temperature