Chamber formation and morphogenesis in the developing mammalian heart

In this study we challenge the generally accepted view that cardiac chamber s form from an array of segmental primordia arranged along the anteroposter ior axis of the linear and looping heart tube. We traced the spatial patter n of expression of genes encoding atrial natriuretic factor, sarcoplasmic r eticulum calcium ATPase, Chisel, Irx5, Irx4, myosin light chain 2v, and bet a-myosin heavy chain and related these to morphogenesis. Based on the patte rns we propose a two-step model for chamber formation in the embryonic hear t. First, a linear heart forms, which is composed of "primary" myocardium t hat nonetheless shows polarity in phenotype and gene expression along its a nteroposterior and dorsoventral axes. Second, specialized ventricular chamb er myocardium is specified at the ventral surface of the linear heart tube, while distinct left and right atrial myocardium forms more caudally on lat erodorsal surfaces. The process of looping aligns these primordial chambers such that they face the outer curvature. Myocardium of the inner curvature , as well as that of inflow tract, atrioventricular canal, and outflow trac t, retains the molecular signature originally found in linear heart tube my ocardium. Evidence for distinct transcriptional programs which govern compa rtmentalization in the forming heart is seen in the patterns of expression of Hand1 for the dorsoventral axis, Irx4 and Tbx5 for the anteroposterior a xis, and Irx5 for the distinction between primary and chamber myocardium. ( C) 2000 Academic Press.