Zebrafish Hearts and Minds: Nodal Signaling in Cardiac and Neural Left-Right Asymmetry

The establishment of the left–right (L-R) axis is essential for the correct development of the cardiovascular system; for instance, for heart looping and for the asymmetric remodeling of the aortic arches (for review, seeCapdevila et al. 2000). Consequently, defects in L-R patterning can give rise to congenital defects of the heart andthe vasculature (Ferencz et al. 1997). Because of its rapiddevelopment, transparency, and genetic tractability, thezebrafish has proven to be a useful model system inwhich to study cardiovascular development. Many earlyaspects of heart formation appear to be similar betweenthe zebrafish and other vertebrates. An embryonic zebrafish heart is analogous in key respects to the heart of ahuman embryo at about 3 weeks postimplantation (for review, see Driever and Fishman 1996). The embryonic zebrafish heart also resembles other hearts in that it undergoes the same rightward looping (D-looping) as is seenfor the hearts of mammals and other vertebrates. Thus,studies in the zebrafish can provide insight into the earlyL-R patterning processes that are involved in the development of all vertebrate hearts. In addition, zebrafish isthe only model system in which the development of diencephalic and visceral organ asymmetry can be analyzedconcurrently. This makes the zebrafish system especiallywell-suited to addressing the issue of whether and howbrain and cardiac/visceral L-R asymmetry are coordinated or linked. In this paper, we summarize progressmade in analyzing cardiac L-R asymmetry in the zebrafish as well as the broader issue of how L-R asymmetry in the cardiovascular system is coordinated with theL-R morphogenesis of other organs...