The polarity protein Dlg5 regulates collective cell migration during Drosophila oogenesis

PLoS One. 2019 Dec 19;14(12):e0226061. doi: 10.1371/journal.pone.0226061. eCollection 2019.

Abstract

Collective migration plays critical roles in animal development, physiological events, and cancer metastasis. However, the molecular mechanisms of collective cell migration are not well understood. Drosophila border cells represent an excellent in vivo genetic model to study collective cell migration and identify novel regulatory genes for cell migration. Using the Mosaic Analysis with a Repressible Cell Marker (MARCM) system, we screened 240 P-element insertion lines to identify essential genes for border cell migration. Two genes were uncovered, including dlg5 (discs large 5) and CG31689. Further analysis showed that Dlg5 regulates the apical-basal polarity and cluster integrity in border cell clusters. Dlg5 is enriched in lateral surfaces between border cells and central polar cells but also shows punctate localization between border cells. We found that the distribution of Dlg5 in border cell clusters is regulated by Armadillo. Structure-function analysis revealed that the N-terminal Coiled-coil domain and the C-terminal PDZ3-PDZ4-SH3-GUK domains but not the PDZ1-PDZ2 domains of Dlg5 are required for BC migration. The Coiled-coil domain and the PDZ4-SH3-GUK domains are critical for Dlg5's cell surface localization in border cell clusters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Armadillo Domain Proteins / metabolism
  • Cell Membrane / metabolism
  • Cell Movement
  • Cell Polarity
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Genes, Reporter
  • Guanylate Kinases / antagonists & inhibitors
  • Guanylate Kinases / chemistry
  • Guanylate Kinases / metabolism*
  • Oogenesis*
  • Ovum / growth & development
  • Ovum / metabolism
  • Protein Domains
  • Protein Kinase C / metabolism
  • RNA Interference
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / metabolism

Substances

  • ARM protein, Drosophila
  • Armadillo Domain Proteins
  • Dlg5 protein, Drosophila
  • Drosophila Proteins
  • PSI protein, Drosophila
  • RNA-Binding Proteins
  • Transcription Factors
  • Protein Kinase C
  • aPKC protein, Drosophila
  • Guanylate Kinases

Grants and funding

This work is supported by grants from National Natural Sciences Foundation of China (31571435, 31271488, 31171335) to JC and Starting Research Fund from Shangrao Normal University (K6000333) to JL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.