Grhl3 promotes retention of epidermal cells under endocytic stress to maintain epidermal architecture in zebrafish

PLoS Genet. 2021 Sep 27;17(9):e1009823. doi: 10.1371/journal.pgen.1009823. eCollection 2021 Sep.

Abstract

Epithelia such as epidermis cover large surfaces and are crucial for survival. Maintenance of tissue homeostasis by balancing cell proliferation, cell size, and cell extrusion ensures epidermal integrity. Although the mechanisms of cell extrusion are better understood, how epithelial cells that round up under developmental or perturbed genetic conditions are reintegrated in the epithelium to maintain homeostasis remains unclear. Here, we performed live imaging in zebrafish embryos to show that epidermal cells that round up due to membrane homeostasis defects in the absence of goosepimples/myosinVb (myoVb) function, are reintegrated into the epithelium. Transcriptome analysis and genetic interaction studies suggest that the transcription factor Grainyhead-like 3 (Grhl3) induces the retention of rounded cells by regulating E-cadherin levels. Moreover, Grhl3 facilitates the survival of MyoVb deficient embryos by regulating cell adhesion, cell retention, and epidermal architecture. Our analyses have unraveled a mechanism of retention of rounded cells and its importance in epithelial homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endocytosis*
  • Epidermal Cells / cytology
  • Epidermal Cells / metabolism*
  • Mutation
  • Stress, Physiological*
  • Transcriptome
  • Up-Regulation
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*

Substances

  • GRHL3 protein, zebrafish
  • Zebrafish Proteins

Grants and funding

This research was supported by funds from Wellcome trust-DBT India Alliance (500129-Z-09-Z) and TIFR-DAE (RTI4003;12P-121) to MS and Council of Scientific and Industrial Research (SPM fellowship) to MP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.