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Updated: Aug 14, 2026
A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse
Published on: December 16, 2022
Left-right lineage analysis of AV cushion tissue in normal and laterality defective Xenopus hearts
Ann F Ramsdell1, Jayne M Bernanke, John Johnson
1Department of Cell and Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA. ramsdell@musc.edu
Insights
Laterality disease in embryos can cause congenital heart defects due to abnormal development of atrioventricular canal cushions. This study reveals defective left-right cell patterning in these crucial heart structures.
Area of Science:
- Developmental Biology
- Cardiovascular Science
- Genetics
Background:
- Complex congenital heart defects often occur in individuals with laterality disease.
- Valvuloseptal defects are common in these patients, suggesting a link to embryonic heart development.
- The atrioventricular (AV) canal cushions are progenitor tissues for mature heart valves and septa.
Purpose of the Study:
- To investigate the hypothesis that defective left-right patterning of AV canal cushions contributes to valvuloseptal defects in laterality disease.
- To analyze cell lineage and tissue formation in the AV canal during embryonic development.
Main Methods:
- Utilized Xenopus laevis embryos for left-right lineage analysis of AV canal myocytes and mesenchyme cells.
- Experimentally induced laterality mutants by misexpressing ALK4, a TGF-beta receptor involved in left-right axis determination.
- Compared cell lineage composition and tissue amount in wild-type versus mutant embryos.
Main Results:
- A majority of ALK4-induced laterality mutant embryos exhibited abnormalities in AV canal cushion amount and left-right cell lineage composition.
- Significant variation in these abnormalities was observed even among embryos with the same body situs.
- Defective cell allocation within the AV canal was evident.
Conclusions:
- Abnormalities in the amount and left-right origin of cells in AV canal cushions are linked to valvuloseptal defects.
- Defective cell allocation in the AV canal may causally contribute to the high incidence of these heart defects in laterality disease.
- This research provides insights into the morphogenesis of valvuloseptal structures and their association with laterality disorders.
Abstract:
The majority of complex congenital heart defects occur in individuals who are afflicted by laterality disease. We hypothesize that the prevalence of valvuloseptal defects in this population is due to defective left-right patterning of the embryonic atrioventricular (AV) canal cushions, which are the progenitor tissue for valve and septal structures in the mature heart. Using embryos of the frog Xenopus laevis, this hypothesis was tested by performing left-right lineage analysis of myocytes and cushion mesenchyme cells of the superior and inferior cushion regions of the AV canal. Lineage analyses were conducted in both wild-type and laterality mutant embryos experimentally induced by misexpression of ALK4, a type I TGF-beta receptor previously shown to modulate left-right axis determination in Xenopus. We find that abnormalities in overall amount and left-right cell lineage composition are present in a majority of ALK4-induced laterality mutant embryos and that much variation in the nature of these abnormalities exists in embryos that exhibit the same overall body situs. We propose that these two parameters of cushion tissue formation-amount and left-right lineage origin-are important for normal processes of valvuloseptal morphogenesis and that defective allocation of cells in the AV canal might be causatively linked to the high incidence of valvuloseptal defects associated with laterality disease.
