Endothelial versus pronephron fate decision is modulated by the transcription factors Cloche/Npas4l, Tal1, and Lmo2
Year: 2022
Type: article
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 genesetsrp,tal1, andlmo2. We generated a knock-in reporter in zebrafishnpas4lto visualize endothelial progenitors and their derivatives in wild-type and mutant embryos. Unexpectedly, we find that innpas4lmutants,npas4lreporter–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 ofnpas4lreporter–expressing cells to pronephron tubules is also observed intal1andlmo2mutants and is reversed innpas4lmutants injected withtal1mRNA. Together, these data reveal that Npas4l/Tal1/Lmo2 regulate the fate decision between the endothelial and pronephron lineages.
Source: Science Advances
Institutions: Max Planck Institute for Heart and Lung Research, German Centre for Cardiovascular Research, German Center for Lung Research, Cardio-Pulmonary Institute, University of Colorado Anschutz, University of Colorado Denver, Center for Regenerative Therapies Dresden, Technische Universität Dresden, Goethe University Frankfurt, Senckenberg Biodiversity and Climate Research Centre, LOEWE Centre for Translational Biodiversity Genomics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4293783069