Genetically encoded tension heterogeneity sculpts cardiac trabeculation.

Abstract

The myocardial wall arises from a single layer of cardiomyocytes, some delaminate to create trabeculae while others remain in the compact layer. However, the mechanisms governing cardiomyocyte fate decisions remain unclear. Using single-cell RNA sequencing, genetically encoded biosensors, and in toto live imaging, we observe intrinsic variations in <i>erbb2</i> expression and its association with trabecular fate. Specifically, <i>erbb2</i> promotes PI3K activity and recruits the Arp2/3 complex, inducing a polarized accumulation of the actomyosin network to drive cell delamination. Subsequently, the lineage-committed nascent trabeculae trigger Notch activity in neighboring cardiomyocytes to suppress <i>erbb2</i> expression and reduce cell tension, thereby confining them to the compact layer. Overall, this genetic and cellular interplay governs compact and trabecular cell fate determination to orchestrate myocardial pattern formation.