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Foxj1 regulates asymmetric gene expression during left-right axis patterning in mice
Min Zhang1, Mary F Bolfing, Heather J Knowles
1Developmental Biology Research Unit, The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Biochemical and Biophysical Research Communications
|October 27, 2004
Summary
The transcription factor Foxj1 is crucial for establishing the left-right body axis in mouse embryos. Its absence disrupts normal embryonic development, leading to randomized gene expression and cardiac looping defects.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- The establishment of left-right asymmetry is fundamental for proper embryonic development.
- The transcription factor Foxj1 plays a role in embryonic development, but its precise function in left-right axis patterning is not fully understood.
- Cilia, particularly motile 9+2 cilia, are implicated in left-right axis determination.
Purpose of the Study:
- To investigate the role of the transcription factor Foxj1 in left-right axis patterning during mouse embryonic development.
- To determine the impact of Foxj1 deficiency on the expression of key genes involved in asymmetry.
- To examine the presence and type of cilia in the node of Foxj1-deficient embryos.
Main Methods:
- Generation and analysis of mice with a targeted mutation in the Foxj1 gene (foxj1-/-).
- Assessment of embryonic cardiac tube looping (dextral/D-looping vs. sinistral/L-looping).
- Analysis of gene expression patterns for nodal, Pitx2, and Lefty-2.
- Examination of cilia structure (9+2 vs. 9+0) in the embryonic node.
Main Results:
- Foxj1-deficient embryos exhibit randomized D- or L-looping of the embryonic cardiac tube.
- Foxj1 is expressed in ventral node cells preceding asymmetric gene expression.
- While 9+2 cilia are absent, 9+0 cilia are present in the node of foxj1-/- embryos.
- Expression patterns of nodal and Pitx2 are randomized in foxj1-/- embryos.
- Lefty-2 expression is completely absent in foxj1-/- embryos at the early somite stage.
Conclusions:
- Foxj1 acts early in the process of left-right axis patterning.
- Foxj1 regulates the asymmetric expression of key developmental genes, including nodal, Pitx2, and Lefty-2.
- The observed effects are not due to a direct interaction between Foxj1 and the examined genes.
- Foxj1's role in establishing left-right asymmetry is independent of 9+2 cilia but may involve 9+0 cilia.