Insights Into Contractility and Laminin Dependent Cardiac Morphogenesis in Zebrafish: A Role for the Extracellular Matrix?

During embryonic development, the heart undergoes complex morphogenesis alongside significant growth driven by addition of cells from a conserved progenitor population called the Second Heart Field (SHF). Timely migration of these cells into the developing heart is crucial for its development, and mutations in genes driving this process are linked with heart defects in humans. Cardiac morphogenesis also requires the timely deposition, regionalisation and degradation of the cardiac extracellular matrix (ECM). Within this ECM, Laminins in the basement membrane provide key links between tissues and the extracellular environment. Additionally, the heart is beating during its morphogenesis, however the extent to which Laminin and contractility control regionalisation of the ECM, and how this influences SHF addition, is poorly understood.

Consequently, we characterised morphological changes in the developing zebrafish heart and cardiac ECM, in loss of contractility (tnnt2a) and loss of Laminin (lamb1a) models. Our results so far show an overexpansion of ECM in loss of contractility models, as well as reductions in heart volume and looping, whereas lamb1a mutants show regionalised expansions in cardiac ECM, particularly in the atrium. These results suggest crucial roles for contractility and Laminin in mediating cardiac morphogenesis, via changes to regionalisation of the cardiac ECM. Additionally, analysis of video of contracting hearts revealed changes in cardiomyocyte velocity in lamb1a embryos, suggesting that Laminin may also shape contractile mechanics of the developing heart.

We also observed reductions in cell counts in loss of contractility models, suggesting that contractility may play a crucial role in the rate of addition of cells from the Second Heart Field. Finally, we also discuss some of the recent data acquired at our lab using the ZEISS LSM Lightfield 4D system, and our own perspectives on the application of this system to our research. Join our upcoming webinar to learn more.