Differential expression of flectin in the extracellular matrix and left-right asymmetry in mouse embryonic heart during looping stages.

A novel extracellular matrix protein flectin (250 kD M(r)) shows specific left-right asymmetric expression before and throughout the looping process during heart development in avian embryos [Tsuda et al., 1996]. Flectin is a candidate molecule to provide directionality to the looping process in the avian model. In this study on mouse embryonic heart development, flectin is shown to be developmentally regulated and to be expressed in a specific asymmetric fashion, but in a different pattern from that observed in avian hearts. The molecules involved in development tend to be the same, but timing of expression, modulation, and asymmetry are different. In the mouse embryo, flectin is expressed symmetrically when the cardiogenic plate is formed. As looping progresses, flectin expression becomes asymmetric. There is right side predominance at the outflow tract and left side predominance at the ventricular portion of the tubular heart. The left side predominance of flectin develops in an anteroposterior direction, while right side predominance of the outflow tract remains relatively unchanged. These differential expression patterns of flectin decrease once the looping process is completed. After looping, flectin becomes restricted to the epicardium and subepicardial extracellular regions. In inv/inv mice, a known mouse model for human situs inversus, in which the directionality of heart looping is inverted, flectin expression pattern is mirror image of that of normal mouse embryos during looping stages. Our study indicates that, in the mouse, flectin shows a specific asymmetric expression pattern after initiation of heart looping and that this asymmetric expression pattern is related to the directionality of looping. The remodeling of the extracellular matrix (ECM) including specific flectin expression begins with the looping process. This morphogenetic change of the ECM coincides with the differentiation of each region of the tubular heart.