Abstract: In early heart development, bilateral fields of heart progenitor cells (HPCs) undergo a large-scale movement from the anterior lateral plate mesoderm to merge on the ventral midline, undergoing a mesenchymal-to-epithelial transition (MET) halfway through this process. While the heart is the first functioning organs in the developing embryo, a comprehensive model for early heart development that integrates both physical mechanisms and molecular signaling pathways remains elusive. Here, we utilize Xenopus embryos to investigate the role of mechanical cues in driving MET in HPCs and show how dysregulation of these cues can cause congenital heart defects (CHDs). From this integrated analysis of HPC polarity and mechanics, we propose that normal heart development requires HPCs to undergo a critical behavioral and phenotypic transition on their way to the ventral midline and that this transition is driven in response to the changing mechanical properties of their endoderm substrate. We conclude that the etiology underlying many CHDs may involve errors in mechanical signaling and MET.
Tim can be found in his new position in R&D at Essen Biosciences (now Sartorius).