Cellular and Molecular Mechanisms of Cardiac Chamber Maturation in Zebrafish

Abstract

The formation of the heart is a critical part of development that, if defective, can lead to congenital malformations incompatible with life. An improved understanding of the cellular and molecular processes that build the heart is essential to elucidate the causes of congenital defects and to design appropriate therapies. Relatively little is known about how the cardiac chambers adopt distinct forms to follow their specialized functions. Here, I have used a multicolor genetic labeling system to trace the progeny of zebrafish atrial cardiomyocytes as they expand to form the mature atrial myocardium. By comparing the observed cellular dynamics to those previously mapped in the ventricle, I identified characteristics of chamber development, including wall thickening, wall composition, and internal muscle formation, that contribute to the structural divergence of the chambers. As coronary vessel formation is one such chamber-specific morphogenetic process, I then explored the effect of a chamber-specific growth factor on cardiac development and homeostasis. Using a transgenic reporter and an inducible overexpression tools, I found ectopic expression of this growth factor stimulates cardiomyocyte proliferation. However, overexpression also blocks regeneration, possibly due to the abolition of an endogenous gradient localized to the site of injury. These findings not only provide new details for how the cardiac chambers form, but also demonstrate how understanding developmental phenomena can provide insights into important concepts of regenerative medicine.