PUBLICATION
Wnt Signaling Positively Regulates Endothelial Cell Fate Specification in the Fli1a-Positive Progenitor Population via Lef1
- Authors
- Hübner, K., Grassme, K.S., Rao, J., Wenke, N.K., Zimmer, C.L., Korte, L., Mu Ller, K., Sumanas, S., Greber, B., Herzog, W.
- ID
- ZDB-PUB-170817-8
- Date
- 2017
- Source
- Developmental Biology 430(1): 142-155 (Journal)
- Registered Authors
- Grassme, Kathrin, Herzog, Wiebke, Sumanas, Saulius
- Keywords
- Primitive hematopoiesis, Wnt reporter, mesoderm, vasculogenesis, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Count
- Cell Differentiation
- Cell Line
- Cell Lineage*
- Endothelial Cells/cytology*
- Endothelial Cells/metabolism*
- Erythrocytes/cytology
- Erythrocytes/metabolism
- Human Embryonic Stem Cells/cytology
- Human Embryonic Stem Cells/metabolism
- Humans
- Mesoderm/cytology
- Mesoderm/metabolism
- Models, Biological
- Organogenesis
- Somites/embryology
- Somites/metabolism
- Transcription Factors/metabolism*
- Wnt Signaling Pathway*
- Wnt3A Protein/metabolism
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- beta Catenin/metabolism
- PubMed
- 28811218 Full text @ Dev. Biol.
Citation
Hübner, K., Grassme, K.S., Rao, J., Wenke, N.K., Zimmer, C.L., Korte, L., Mu Ller, K., Sumanas, S., Greber, B., Herzog, W. (2017) Wnt Signaling Positively Regulates Endothelial Cell Fate Specification in the Fli1a-Positive Progenitor Population via Lef1. Developmental Biology. 430(1):142-155.
Abstract
During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2BAC:Venus-Pest)mu288; Tg(14TCF:loxP-STOP-loxP-dGFP)mu202). We therefore can detect β-catenin dependent Wnt signaling activity in a subset of the Fli1a-positive progenitor population. Additionally, we show that mesodermal Wnt3a-mediated signaling via the transcription factor Lef1 positively regulates EC specification (defined by kdrl expression) at the expense of primitive erythrocyte specification (defined by gata1 expression) in zebrafish embryos. Using mesoderm derived from human embryonic stem cells, we identified the same principle of Wnt signaling dependent EC specification in conjunction with auto-upregulation of LEF1. Our data indicate a novel role of β-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping