An embryonic system to assess direct and indirect Wnt transcriptional targets

Sci Rep. 2017 Sep 11;7(1):11092. doi: 10.1038/s41598-017-11519-z.

Abstract

During animal development, complex signals determine and organize a vast number of tissues using a very small number of signal transduction pathways. These developmental signaling pathways determine cell fates through a coordinated transcriptional response that remains poorly understood. The Wnt pathway is involved in a variety of these cellular functions, and its signals are transmitted in part through a β-catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that can be used to distinguish between activation, de-repression and repression of transcriptional responses, separating upstream and downstream pathway activation and canonical/non-canonical Wnt signals in embryos. We find specific sets of genes downstream of both β-catenin and TCF with an additional group of genes regulated by Wnt, while the non-canonical Wnt4 regulates a separate cohort of genes. We correlate transcriptional changes with phenotypic outcomes of cell differentiation and embryo size, showing our model can be used to characterize developmental signaling compartmentalization in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Computational Biology / methods
  • Drosophila / embryology
  • Drosophila / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Mutation
  • Phenotype
  • Protein Binding
  • Transcriptional Activation*
  • Transcriptome
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway

Substances

  • Wnt Proteins