PUBLICATION
Interaction of retinoic acid and scl controls primitive blood development
- Authors
- de Jong, J.L., Davidson, A.J., Wang, Y., Palis, J., Opara, P., Pugach, E., Daley, G.Q., and Zon, L.I.
- ID
- ZDB-PUB-100427-8
- Date
- 2010
- Source
- Blood 116(2): 201-209 (Journal)
- Registered Authors
- Davidson, Alan, de Jong, Jill, Opara, Praise, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism*
- Cell Differentiation/genetics
- Embryo, Nonmammalian
- GATA1 Transcription Factor/genetics
- GATA1 Transcription Factor/metabolism
- Gene Expression
- Gene Expression Regulation, Developmental*
- Hematopoiesis/genetics*
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism
- In Situ Hybridization
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins/metabolism*
- Tretinoin/metabolism*
- Zebrafish/embryology
- Zebrafish/physiology*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 20410509 Full text @ Blood
Citation
de Jong, J.L., Davidson, A.J., Wang, Y., Palis, J., Opara, P., Pugach, E., Daley, G.Q., and Zon, L.I. (2010) Interaction of retinoic acid and scl controls primitive blood development. Blood. 116(2):201-209.
Abstract
Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation. Here we demonstrate that RA decreases gata1 expression and blocks primitive hematopoiesis in zebrafish (Danio rerio) embryos, while increasing expression of the vascular marker, fli1. Treatment with an inhibitor of RA biosynthesis or a retinoic acid receptor antagonist increases gata1(+) erythroid progenitors in the posterior mesoderm of wild type embryos and anemic cdx4(-/-) mutants, indicating a link between the cdx-hox signaling pathway and RA. Overexpression of scl, a DNA binding protein necessary for hematopoietic development, rescues the block of hematopoiesis induced by RA. We show these effects of RA and RA pathway inhibitors are conserved during primitive hematopoiesis in murine yolk sac explant cultures and embryonic stem cell assays. Taken together, these data indicate that RA inhibits the commitment of mesodermal cells to hematopoietic fates, functioning downstream of cdx4 and upstream of scl. Our studies establish a new connection between RA and scl during development that may participate in stem cell self-renewal and hematopoietic differentiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping