Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity

Cell. 2019 Mar 7;176(6):1379-1392.e14. doi: 10.1016/j.cell.2019.01.019. Epub 2019 Feb 14.

Abstract

Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. Conversely, MPC specification is defective in taz-/- follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity.

Keywords: YAP/TAZ; cell fate specification; lateral inhibition; morphogenesis; oogenesis; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Communication / physiology
  • Cell Differentiation / physiology
  • Cell Lineage
  • Cell Nucleus / metabolism
  • Female
  • Granulosa Cells / metabolism
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Oocytes / metabolism
  • Oocytes / physiology
  • Oogenesis / physiology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcriptional Activation / physiology
  • Zebrafish / metabolism
  • Zebrafish Proteins / antagonists & inhibitors
  • Zebrafish Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Transcription Factors
  • WWTR1 protein, zebrafish
  • Zebrafish Proteins
  • Protein-Serine-Threonine Kinases