Essential roles for Cdx in murine primitive hematopoiesis
Travis Brooke-Bisschop1, Joanne G A Savory1, Tanya Foley1
1Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
Developmental Biology
|January 10, 2017
Summary
Transcription factors Cdx1 and Cdx2 are crucial for primitive hematopoiesis in mice. Their combined loss impairs blood development and yolk sac vasculature by affecting the Scl/Tal1 gene.
Area of Science:
- Developmental Biology
- Hematopoiesis
- Gene Regulation
Background:
- Cdx transcription factors are vital for primitive hematopoiesis in zebrafish, regulating hox genes.
- Murine models show hematopoietic defects in Cdx mutants, but a zebrafish-like phenotype was lacking due to functional redundancy and early lethality.
Purpose of the Study:
- To investigate the impact of combined Cdx1 and Cdx2 loss on murine primitive hematopoiesis.
- To establish a mouse model that reflects the hematopoietic phenotype observed in zebrafish Cdx mutants.
Main Methods:
- Utilized Cre-mediated conditional deletion to generate Cdx1/Cdx2 double mutants.
- Analyzed primitive hematopoiesis and yolk sac vasculature in the generated mutants.
- Performed chromatin immunoprecipitation to assess Cdx2 binding to Scl.
- Evaluated rescue of hematopoietic defects via exogenous Scl expression.
Main Results:
- Cdx1/Cdx2 double mutants displayed defects in primitive hematopoiesis and yolk sac vasculature.
- Expression of hematopoietic transcription factors, including Scl/Tal1, was reduced in mutants.
- Cdx2 was found to occupy Scl in vivo.
- Exogenous Scl expression rescued hematopoietic and yolk sac differentiation defects.
Conclusions:
- Cdx1 and Cdx2 play critical, upstream roles in murine primitive hematopoiesis.
- The Cdx-Scl regulatory axis is essential for early blood development.
- This study provides a novel mouse model for studying Cdx-mediated hematopoiesis.
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