N-cadherin stabilises neural identity by dampening anti-neural signals

Karolina Punovuori, Rosa P. Migueles, Mattias Malaguti, Guillaume Blin, Kenneth G. MacLeod, Neil O. Carragher, Tim Pieters, Frans van Roy, Marc P. Stemmler, Sally Lowell

Research output: Contribution to journalArticlepeer-review

Abstract

A switch from E- to N-cadherin regulates the transition from pluripotency to neural identity, but the mechanism by which cadherins regulate differentiation was previously unknown. Here we show that the acquisition of N-cadherin stabilises neural identity by dampening anti-neural signals. We use quantitative image-analysis to identify an effect of N-cadherin to promote neural differentiation independently of effects on cell cohesiveness. We reveal that cadherin switching diminishes the level of nuclear β-catenin, and that N-cadherin also dampens FGF activity and consequently stabilises neural fate. Finally, we compare the timing of cadherin switching and differentiation in vivo and in vitro, and find that this process becomes dysregulated during in vitro differentiation. We propose that N-cadherin helps to propagate a stable neural identity throughout the emerging neuroepithelium, and that dysregulation of this process contributes to asynchronous differentiation in culture.
Original languageEnglish
Article number dev183269
JournalDevelopment
Volume146
Issue number21
Early online date10 Oct 2019
DOIs
Publication statusPublished - 8 Nov 2019

Keywords

  • Cadherin
  • FGF
  • Neural development
  • Pluripotent
  • Wnt
  • Mouse

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