PUBLICATION
Somite-Derived Retinoic Acid Regulates Zebrafish Hematopoietic Stem Cell Formation
- Authors
- Pillay, L.M., Mackowetzky, K.J., Widen, S.A., Waskiewicz, A.J.
- ID
- ZDB-PUB-161120-3
- Date
- 2016
- Source
- PLoS One 11: e0166040 (Journal)
- Registered Authors
- Waskiewicz, Andrew
- Keywords
- Embryos, Gene expression, Aorta, Zebrafish, Hematopoietic stem cells, In situ hybridization, Notch signaling, Somites
- MeSH Terms
- none
- PubMed
- 27861498 Full text @ PLoS One
Citation
Pillay, L.M., Mackowetzky, K.J., Widen, S.A., Waskiewicz, A.J. (2016) Somite-Derived Retinoic Acid Regulates Zebrafish Hematopoietic Stem Cell Formation. PLoS One. 11:e0166040.
Abstract
Hematopoietic stem cells (HSCs) are multipotent progenitors that generate all vertebrate adult blood lineages. Recent analyses have highlighted the importance of somite-derived signaling factors in regulating HSC specification and emergence from dorsal aorta hemogenic endothelium. However, these factors remain largely uncharacterized. We provide evidence that the vitamin A derivative retinoic acid (RA) functions as an essential regulator of zebrafish HSC formation. Temporal analyses indicate that RA is required for HSC gene expression prior to dorsal aorta formation, at a time when the predominant RA synthesis enzyme, aldh1a2, is strongly expressed within the paraxial mesoderm and somites. Previous research implicated the Cxcl12 chemokine and Notch signaling pathways in HSC formation. Consequently, to understand how RA regulates HSC gene expression, we surveyed the expression of components of these pathways in RA-depleted zebrafish embryos. During somitogenesis, RA-depleted embryos exhibit altered expression of jam1a and jam2a, which potentiate Notch signaling within nascent endothelial cells. RA-depleted embryos also exhibit a severe reduction in the expression of cxcr4a, the predominant Cxcl12b receptor. Furthermore, pharmacological inhibitors of RA synthesis and Cxcr4 signaling act in concert to reduce HSC formation. Our analyses demonstrate that somite-derived RA functions to regulate components of the Notch and Cxcl12 chemokine signaling pathways during HSC formation.
Errata / Notes
Correction: Somite-Derived Retinoic Acid Regulates Zebrafish Hematopoietic Stem Cell Formation
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping