Dynamics of Drosophila endoderm specification

Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2112892119. doi: 10.1073/pnas.2112892119. Epub 2022 Apr 11.

Abstract

During early Drosophila embryogenesis, a network of gene regulatory interactions orchestrates terminal patterning, playing a critical role in the subsequent formation of the gut. We utilized CRISPR gene editing at endogenous loci to create live reporters of transcription and light-sheet microscopy to monitor the individual components of the posterior gut patterning network across 90 min prior to gastrulation. We developed a computational approach for fusing imaging datasets of the individual components into a common multivariable trajectory. Data fusion revealed low intrinsic dimensionality of posterior patterning and cell fate specification in wild-type embryos. The simple structure that we uncovered allowed us to construct a model of interactions within the posterior patterning regulatory network and make testable predictions about its dynamics at the protein level. The presented data fusion strategy is a step toward establishing a unified framework that would explore how stochastic spatiotemporal signals give rise to highly reproducible morphogenetic outcomes.

Keywords: Drosophila development; data integration; gene regulatory networks; image registration; transcriptomics.

MeSH terms

  • Animals
  • Body Patterning* / genetics
  • Drosophila Proteins* / genetics
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / growth & development
  • Endoderm* / growth & development
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks*

Substances

  • Drosophila Proteins