Genetic Dissection of Heart Development
109
The application of the zebrafish system to dissect pathways of functional development of the heart is discussed elsewhere (Warren and
Fishman 1998). In this review, we focus on three issues of heart formation. At the cellular level, we focus on tracking the localization of
cardiac precursors at various developmental stages and identifying the
tissues and factors affecting cardiac cell fate determination. At the organ
level, we focus on cardiac chamber formation. At the embryo level, we
will discuss the embryonic left-right influence on the heart. Finally, we
will discuss the prospects for applying the zebrafish system to studying
organogenesis.
7.2 Heart Field
Although mesodermal in origin, myocyte migration paths differ among
species. For example, in Drosophila, the mesodermal precursors, including the heart, are originated ventrally and later migrate and become
specified at dorsal sites (Azpiazu and Frasch 1993; Bodmer 1993). In
Xenopus, the heart precursors originate from the dorsolateral tissues and
migrate ventrally (for review see Fishman and Chien 1997). Prior to
formation of the primitive heart mesoderm, myocytes reside lateral to
the midline from where they fuse (at the midline) and form the heart.
In the zebrafish, the location and the migratory path of the cardiac
precursors have been traced embryologically by single cell injection
lineage-tracing technique (Stainier et al. 1993). The cardiac precursors
are localized at the margin of the ventral hemisphere of the· zebrafish
embryo as early as the blastula stage. The most ventrally localized cells
have the highest probability of contributing to the heart, a property
which diminishes toward the dorsal side. Some of the progeny of the
ventral blastomeres involute during gastrulation, migrate toward the
embryonic midline in the lateral plate and eventually populate the heart
(Stainier et al. 1993).
Nkx2.5 is a vertebrate homologue of the Drosophila homeodomain
gene tinman. Mutation in tinman results in defective heart formation
(Bodmer 1993). In all vertebrates analyzed including, fish, frog, chick,
and mouse, Nkx2.5 is expressed in a region which at least overlaps with
the position of lineage-derived cardiac precursors (for review see
Harvey 1996). Overexpression of Nkx2.5 causes an enlarged heart in the
109
The application of the zebrafish system to dissect pathways of functional development of the heart is discussed elsewhere (Warren and
Fishman 1998). In this review, we focus on three issues of heart formation. At the cellular level, we focus on tracking the localization of
cardiac precursors at various developmental stages and identifying the
tissues and factors affecting cardiac cell fate determination. At the organ
level, we focus on cardiac chamber formation. At the embryo level, we
will discuss the embryonic left-right influence on the heart. Finally, we
will discuss the prospects for applying the zebrafish system to studying
organogenesis.
7.2 Heart Field
Although mesodermal in origin, myocyte migration paths differ among
species. For example, in Drosophila, the mesodermal precursors, including the heart, are originated ventrally and later migrate and become
specified at dorsal sites (Azpiazu and Frasch 1993; Bodmer 1993). In
Xenopus, the heart precursors originate from the dorsolateral tissues and
migrate ventrally (for review see Fishman and Chien 1997). Prior to
formation of the primitive heart mesoderm, myocytes reside lateral to
the midline from where they fuse (at the midline) and form the heart.
In the zebrafish, the location and the migratory path of the cardiac
precursors have been traced embryologically by single cell injection
lineage-tracing technique (Stainier et al. 1993). The cardiac precursors
are localized at the margin of the ventral hemisphere of the· zebrafish
embryo as early as the blastula stage. The most ventrally localized cells
have the highest probability of contributing to the heart, a property
which diminishes toward the dorsal side. Some of the progeny of the
ventral blastomeres involute during gastrulation, migrate toward the
embryonic midline in the lateral plate and eventually populate the heart
(Stainier et al. 1993).
Nkx2.5 is a vertebrate homologue of the Drosophila homeodomain
gene tinman. Mutation in tinman results in defective heart formation
(Bodmer 1993). In all vertebrates analyzed including, fish, frog, chick,
and mouse, Nkx2.5 is expressed in a region which at least overlaps with
the position of lineage-derived cardiac precursors (for review see
Harvey 1996). Overexpression of Nkx2.5 causes an enlarged heart in the