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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Interactions between Cdx genes and retinoic acid modulate early cardiogenesis
Claudia Lengerke1, Rebecca Wingert, Michael Beeretz
1Department of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany. claudia.lengerke@med.uni-tuebingen.de
Developmental Biology
|April 7, 2011
Summary
Cdx transcription factors restrict cardiac cell formation by establishing posterior identity in developing mesodermal cells. These factors, along with the retinoic acid pathway, control early cardiac precursor development.
Area of Science:
- Developmental Biology
- Genetics
Background:
- Cdx transcription factors are essential for embryonic anteroposterior (AP) patterning.
- Cdx1a and Cdx4 redundantly regulate posterior mesodermal derivatives in zebrafish, including blood and kidney development.
Purpose of the Study:
- To investigate the role of Cdx factors in restricting anterior mesodermal derivative formation, specifically cardiac cells.
- To determine if Cdx factors impose posterior identity on mesodermal cells, thereby suppressing cardiac development.
Main Methods:
- Ectopic expression of Cdx1 or Cdx4 in murine embryonic stem cells (ESCs) during mesoderm patterning.
- Assaying cardiac gene expression and embryoid body (EB) formation with beating cell clusters.
- Loss-of-function studies in cdx-deficient zebrafish embryos.
- Analyzing the expansion of anterior-lateral plate mesoderm (giving rise to cardiac progenitors) and retinoic acid (RA) pathway interactions.
Main Results:
- Ectopic Cdx1/Cdx4 expression in differentiating ESCs significantly suppressed cardiac development.
- Loss-of-function in cdx-deficient zebrafish embryos led to a dose-dependent expansion of cardiac progenitor populations.
- Further cardiac development in cdx mutants required additional suppression of the retinoic acid (RA) pathway.
Conclusions:
- Cdx proteins play a crucial role in restricting cardiogenesis by regulating the formation of cardiogenic mesoderm.
- Cdx factors and the RA pathway interact to control the early development of cardiac precursor cells.
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