Tbx5 in Xenopus heart development

The heart is one of the first organs to develop and function in vertebrate embryos. In general, cardiac tissue is specified by inductive signals in the early gastrula that act on precardiac mesoderm as it migrates into the heart field, located at anteriorlateral positions on both sides of the embryo. These nascent cardiac tissues then migrate toward the ventral midline of the body where they fuse to form the heart tube. Rythmic contractions of the heart tube begin soon after its formation, followed by looping and septation of the tube as it completes morphogenesis (DeHaan, 1965; Fishman and Chien, 1997; Jacobson, 1961; Wilens, 1955). In Xenopusembryos, the heart arises from the dorsolateral mesoderm adjacent to the Spemann Organizer (dorsal blastopore lip; Nieuwkoop and Faber stage 10.5; Keller, 1976). Cardiac tissue is specified during gastrulation within the dorsolateral mesoderm by inductive signals from the organizer and the deep dorsoanterior endoderm. Convergent-extension movements bring the paired, precardiac mesoderm into the anterior lateral plate. The bilateral cardiac primordia then migrate ventrally during neurula and early tadpole phases of development (stages 17-28) (Wilens, 1955). Heart tissue is fully specified within the anterior/lateral cardiac field by late neurulation as explants of these regions will form beating tissue when cultured in vitro (Sater and Jacobson, 1990). The migrating cardiac mesoderm fuses at the ventral midline in the stage 28 tailbud tadpole and, by stage 30, a linear heart tube forms consisting of the bulbus cordis, ventricle, atrium and sinus venosus, oriented from anterior to posterior. The heart tube begins beating by stage 35, after which heart septation and looping occur, separating the atrium into right and left halves and reorienting the atria to position them dorsal to the ventricle. In contrast to humans and other mammals, the Xenopusheart has only three chambers: two atria and one ventricle (de Graaf, 1957). The molecular identity of inductive signals that specify the heart are not well understood, but various transcription factors that may regulate cardiac commitment and differentiation have been isolated, and some of these have been directly implicated in the control of cardiac differentiation. Several of these factors are expressed in the anterior lateral mesoderm at the proper time to play a role in heart development, including the Nkx and GATA gene families (Harvey, 1996; Heikinheimo et al., 1994; Jiang and Evans, 1996; Kelley et al., 1993; Laverriere et al., 1994; Morrisey et al., 1996). None of these factors individually have been shown to be sufficient to specify cardiac differentiation or required in the embryo for heart tube formation. Data from overexpression studies and loss-of-function mutations in frogs, zebrafish, mice and humans have demonstrated that Nkx-2.5can induce myocardial gene expression (Cleaver et al., 1996) and that it is necessary for the specification of the right ventricle, heart looping and atrial septation (Lyons et al., 1995; Schott et al., 1998). The GATA factors can induce cardiac gene expression when overexpressed in frog embryos (Jiang and Evans, 1996), and the ventral migration of precardiac mesoderm is disrupted in GATA-4mutant mice. These mutants do, however, form a pair of relatively normal h arts on their left and right sides, indicating that GATA-4is not essential for heart tube formation (Kuo et al., 1997; Molkentin et al., 1997). Other gene families implicated in heart development (Fishman and Olson, 1997; Lyons, 1996; Mohun and Sparrow, 1997) include bHLH factors, MEF2 1739 Development 126, 1739-1751 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV3920