Rationale: The proepicardium (PE) is a transient structure forming at the venous pole of the heart and gives rise to the epicardium, fibroblasts, and smooth muscle cells. The embryological origin of the PE is presently unclear. Asymmetrical formation of the PE on the right inflow tract is a conserved feature of many vertebrate embryos, and in the chicken is under the control of fibroblast growth factor 8 and snail homolog 1.
Objective: To gain further insight into the process of asymmetrical PE formation, we studied the role of TWIST1 during PE formation in the chick embryo.
Methods and results: TWIST1 is asymmetrically expressed on the right side in the somatic mesoderm under the control of snail homolog 1. Fate mapping experiments revealed a contribution of the somatic mesoderm to the PE. After colonization of the heart, this cell lineage gives rise to the epicardium, smooth muscle cells, and potentially fibroblast. Suppression of TWIST1 function in the right coelomic cavity caused a severe disruption of the villous protrusions of the PE and Wilms tumor 1 and transcription factor 21 expression. Rescue with the corresponding mouse cDNA normalized gene expression and PE morphology. Forced expression of TWIST1 on the left side induced ectopic expression domains of Wilms tumor 1 and transcription factor 21.
Conclusions: A significant proportion of the PE has its origin outside of the currently proposed domain in the splanchnic layer of the lateral plate mesoderm. The phenotype in embryos subjected to TWIST1 loss- or gain-of-function suggests an important contribution of somatic mesoderm to the mesothelial cell layer of the PE.
Keywords: developmental biology; epicardium; epithelium; fate mapping; genes, developmental; heart development; mesoderm; pericardium.