Elf5 and Ets2 maintain the mouse extraembryonic ectoderm in a dosage dependent synergistic manner

Dev Biol. 2015 Jan 1;397(1):77-88. doi: 10.1016/j.ydbio.2014.10.011. Epub 2014 Oct 23.

Abstract

The ETS superfamily transcription factors Elf5 and Ets2 have both been implicated in the maintenance of the extraembryonic ectoderm (ExE) of the mouse embryo. While homozygous mutants of either gene result in various degrees of ExE tissue loss, heterozygotes are without phenotype. We show here that compound heterozygous mutants exhibit a phenotype intermediate to that of the more severe Elf5-/- and the milder Ets2-/- mutants. Functional redundancy is shown via commonalities in expression patterns, in target gene expression, and by partial rescue of Elf5-/- mutants through overexpressing Ets2 in an Elf5-like fashion. A model is presented suggesting the functional division of the ExE region into a proximal and distal domain based on gene expression patterns and the proximal to distal increasing sensitivity to threshold levels of combined Elf5 and Ets2 activity.

Keywords: Ectoplacental cone; Elf5; Ets2; Extraembryonic ectoderm; Plac1; Spry4; Trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Animals, Genetically Modified
  • Cattle
  • Cell Differentiation
  • DNA-Binding Proteins / physiology*
  • Ectoderm / physiology*
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Heterozygote
  • Mice
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Proto-Oncogene Protein c-ets-2 / physiology*
  • RNA, Small Interfering / metabolism
  • Time Factors
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • Elf5 protein, mouse
  • Ets2 protein, mouse
  • Proto-Oncogene Protein c-ets-2
  • RNA, Small Interfering
  • Transcription Factors