Lamb1a regulates atrial growth by limiting second heart field addition during zebrafish heart development

Abstract

During early vertebrate heart development, the heart transitions from a linear tube to a complex asymmetric structure, a morphogenetic process that occurs simultaneously with growth of the heart. Cardiac growth during early heart morphogenesis is driven by deployment of cells from the second heart field (SHF) into both poles of the heart. Laminin is a core component of the extracellular matrix and, although mutations in laminin subunits are linked with cardiac abnormalities, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified tissue-specific expression of laminin genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis. Analysis of heart development in lamb1a zebrafish mutant embryos reveals mild morphogenetic defects and progressive cardiomegaly, and that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition. lamb1a mutants exhibit hallmarks of altered haemodynamics, and blocking cardiac contractility in lamb1a mutants rescues heart size and atrial SHF addition. Together, these results suggest that laminin mediates interactions between SHF deployment and cardiac biomechanics during heart morphogenesis and growth in the developing embryo.