Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial...

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Cardiac Anatomy

Background:

• Significant morphological and functional differences exist between the adult human right and left ventricles.
• Epicardium-derived cells, including cardiac fibroblasts and smooth muscle cells, may contribute to these ventricular disparities.
• The relationship between epicardial derivatives and the development of compact ventricular myocardium requires further investigation.

Purpose of the Study:

• To investigate the spatio-temporal contribution of WT-1 and Tcf21 expressing cells to the developing ventricular myocardium.
• To understand the role of these epicardial derivatives in ventricular wall thickening and compaction.
• To explore potential links between developmental patterns and human ventricular morphology.

Main Methods:

• Utilized reporter mice (Wt1CreERT2/+, Tcf21lacZ/+, and PDGFRα-/-;Tcf21LacZ/+) to track WT-1 and Tcf21-expressing cells during heart development.
• Analyzed the distribution patterns of these cell populations within the developing ventricles.
• Assessed ventricular myocardial wall thickness and compaction in wildtype and genetically modified mice.

Main Results:

• WT-1+ cells were initially observed at the inner curvature, right ventricular postero-lateral wall, and left ventricular apical wall, with a greater prevalence in the left ventricle later on.
• Tcf21-LacZ+ cells exhibited a similar distribution but with a delayed appearance compared to WT-1+ cells.
• A gradual increase in myocardial wall thickness was noted earlier in the left ventricle than in the right ventricle.
• PDGFRα-/-;Tcf21LacZ/+ mice displayed deficient epicardium, reduced Tcf21-LacZ+ cells, and impaired ventricular compaction.

Conclusions:

• Spatio-temporal differences in the contribution of WT-1 and Tcf21-LacZ+ cells to the right and left ventricles occur concurrently with myocardial thickening during heart development.
• These developmental patterns may underlie lateralized differences observed in human ventricular morphology and pathology.