Partially compromised specification causes stochastic effects on gut development in C. elegans

Dev Biol. 2017 Jul 1;427(1):49-60. doi: 10.1016/j.ydbio.2017.05.007. Epub 2017 May 11.

Abstract

The C. elegans gut descends from the E progenitor cell through a series of stereotyped cell divisions and morphogenetic events. Effects of perturbations of upstream cell specification on downstream organogenesis have not been extensively investigated. Here we have assembled an allelic series of strains that variably compromise specification of E by perturbing the activation of the gut-specifying end-1 and end-3 genes. Using a marker that allows identification of all E descendants regardless of fate, superimposed with markers that identify cells that have adopted a gut fate, we have examined the fate of E lineage descendants among hundreds of embryos. We find that when specification is partially compromised, the E lineage undergoes hyperplasia accompanied by stochastic and variable specification of gut fate among the E descendants. As anticipated by prior work, the activation of the gut differentiation factor elt-2 becomes delayed in these strains, although ultimate protein levels of a translational ELT-2::GFP reporter resemble those of the wild type. By comparing these effects among the various specification mutants, we find that the stronger the defect in specification (i.e. the fewer number of embryos specifying gut), the stronger the defects in the E lineage and delay in activation of elt-2. Despite the changes in the E lineage in these strains, we find that supernumerary E descendants that adopt a gut fate are accommodated into a relatively normal-looking intestine. Hence, upstream perturbation of specification dramatically affects the E lineage, but as long as sufficient descendants adopt a gut fate, organogenesis overcomes these effects to form a relatively normal intestine.

Keywords: C. elegans; Cell specification; Endoderm; Gene regulatory networks; Hyperplasia; Morphogenesis; Robustness.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation*
  • Cell Division
  • Cell Lineage*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Endoderm / cytology
  • Endoderm / embryology
  • Endoderm / metabolism
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestines / cytology
  • Intestines / embryology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Microscopy, Interference
  • Mutation
  • Stochastic Processes
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • ELT-2 protein, C elegans
  • END-1 protein, C elegans
  • END-3 protein, C elegans
  • GATA Transcription Factors
  • Luminescent Proteins
  • Transcription Factors
  • red fluorescent protein
  • Green Fluorescent Proteins