Endothelial versus pronephron fate decision is modulated by the transcription factors Cloche/Npas4l, Tal1, and Lmo2

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Kenny Mattonet - , Max Planck Institute for Heart and Lung Research (Author)
  • Fréderike W Riemslagh - , University of Colorado Anschutz Medical Campus (Author)
  • Stefan Guenther - , DZHK (German Center for Cardiovascular Research) (Author)
  • Karin D Prummel - , University of Colorado Anschutz Medical Campus (Author)
  • Gokul Kesavan - , Center for Regenerative Therapies Dresden (Author)
  • Stefan Hans - , Center for Regenerative Therapies Dresden (Author)
  • Ingo Ebersberger - , Goethe University Frankfurt (Author)
  • Michael Brand - , Center for Regenerative Therapies Dresden (Author)
  • Alexa Burger - , University of Colorado Anschutz Medical Campus (Author)
  • Sven Reischauer - , Max Planck Institute for Heart and Lung Research (Author)
  • Christian Mosimann - , University of Colorado Anschutz Medical Campus (Author)
  • Didier Y R Stainier - , Max Planck Institute for Heart and Lung Research (Author)

Abstract

Endothelial specification is a key event during embryogenesis; however, when, and how, endothelial cells separate from other lineages is poorly understood. In zebrafish, Npas4l is indispensable for endothelial specification by inducing the expression of the transcription factor genes etsrp, tal1, and lmo2. We generated a knock-in reporter in zebrafish npas4l to visualize endothelial progenitors and their derivatives in wild-type and mutant embryos. Unexpectedly, we find that in npas4l mutants, npas4l reporter-expressing cells contribute to the pronephron tubules. Single-cell transcriptomics and live imaging of the early lateral plate mesoderm in wild-type embryos indeed reveals coexpression of endothelial and pronephron markers, a finding confirmed by creERT2-based lineage tracing. Increased contribution of npas4l reporter-expressing cells to pronephron tubules is also observed in tal1 and lmo2 mutants and is reversed in npas4l mutants injected with tal1 mRNA. Together, these data reveal that Npas4l/Tal1/Lmo2 regulate the fate decision between the endothelial and pronephron lineages.

Details

Original languageEnglish
Article numbereabn2082
Pages (from-to)eabn2082
JournalScience advances
Volume8
Issue number35
Publication statusPublished - 2 Sep 2022
Peer-reviewedYes

External IDs

Scopus 85137048740

Keywords

Research priority areas of TU Dresden

    DFG Classification of Subject Areas according to Review Boards

      Sustainable Development Goals

        ASJC Scopus subject areas