PUBLICATION

Dual role of Jam3b in early hematopoietic and vascular development

Authors
Kobayashi, I., Kobayashi-Sun, J., Hirakawa, Y., Ouchi, M., Yasuda, K., Kamei, H., Fukuhara, S., Yamaguchi, M.
ID
ZDB-PUB-191220-3
Date
2019
Source
Development (Cambridge, England)   147(1): (Journal)
Registered Authors
Fukuhara, Shigetomo, Kobayashi, Isao
Keywords
Hematopoietic stem cells, Junctional adhesion molecule, Mesoderm, Vascular endothelial cells, Zebrafish
MeSH Terms
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cardiovascular System/cytology
  • Cardiovascular System/embryology*
  • Endothelial Cells/physiology
  • Hematopoiesis*/physiology
  • Hematopoietic Stem Cells
  • MAP Kinase Signaling System
  • Mesoderm/embryology
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/physiology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
31852685 Full text @ Development
Abstract
In order to efficiently derive hematopoietic stem cells (HSCs) from pluripotent precursors, it is crucial to understand how mesodermal cells acquire hematopoietic and endothelial identities, two divergent, but closely related cell fates. Although Npas4 has been recently identified as a conserved master regulator of hemato-vascular development, the molecular mechanisms underlying cell fate divergence between hematopoietic and vascular endothelial cells are still unclear. Here, we show in zebrafish that mesodermal cell differentiation into hematopoietic and vascular endothelial cells is regulated by Junctional adhesion molecule 3b (Jam3b) via two independent signaling pathways. Mutation of jam3b led to a reduction in npas4l expression in the posterior lateral plate mesoderm and defects in both hematopoietic and vascular development. Mechanistically, we uncover that Jam3b promotes endothelial specification by regulating npas4l expression through repression of the Rap1a-Erk signaling cascade. Jam3b subsequently promotes hematopoietic development, including HSCs, by regulating lrrc15 expression in endothelial precursors through the activation of an integrin-dependent signaling cascade. Our data provide insight into the divergent mechanisms for instructing hematopoietic or vascular fates from mesodermal cells.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes