Genetic Dissection of Heart Development
111
1995). When the activity of either XNk.x2.3 or XNk.x2.5 alone is blocked
in Xenopus embryos, the heart is mildly affected. However, heart formation is abolished when both Nk.x2.3 and Nk.x2.5 gene activities are
blocked (Fu et al. 1998; Grow and Krieg 1998).
As shown by normal Nk.x2.5 expression in some non-cardiogenic
regions of many species, and the inability of overexpression to cause
complete myogenesis, Nk.x2.5 is insufficient to cause cardiomyocyte
differentiation. One important component may be the persistence past a
certain time of development. In Drosophila, of the many tinman-expressing mesoderm cells, it is only cells which maintain tinman gene
activity which adopt the cardiac fate (Frasch 1995). The expression of
dpp in the adjacent ectoderm is required for maintaining tinman gene
expression. Disruption of dpp activity abolishes tinman gene expression
in the cardioblasts, and therefore abolishes heart formation (Frasch
1995). Unlike other vertebrates studied to date, in the zebrafish, the
Nk.x2.5 expression pattern corresponds to the position of cardiogenic
precursors as early as the onset of gastrulation (Chen and Fishman
1996). At the somitogenesis stage, the Nk.x2.5 expression is restricted to
the lateral plate (Fig. 1). At the time as the bilateral cardiac primordia
fuse at the midline, the lateral mesodermal cells posterior to the notochord turn off Nk.x2.5 expression. As fate-mapped by a laser-based
technique, these cells do not populate the heart. Only the lateral
mesodermal cells anterior to the notochord maintain Nk.x2.5 gene activity and populate the heart (Serbedzija et al. 1998).
Classic embryological experiments showed that at early developmental stages, the embryos can compensate for the loss of organ primordia
(Copenhaver 1924). In the zebrafish, the ability to compensate for loss
of cardiac precursors continues until the heart fuses at the midline
(Serbedzija et al. 1998). Interestingly, the cells transiently expressing
Nk.x2.5 adjacent to the notochord do not appear to contribute to this
regulatory compensation (Serbedzija et al. 1998). Together with the fate
mapping analysis, this implies that the notochord has a negative effect
on heart development. In fact, after the ablation of the tip of the notochord, the adjacent, normally non-cardiac Nk.x2.5 cells do develop the
ability to populate the heart (Goldstein and Fishman 1998).
How does the notochord regulate heart formation? One possibility is
through regulating Nk.x2.5 gene activity via the BMP pathway. In the
notochord-ablated zebrafish embryos, the Nk.x2.5 expression domain
111
1995). When the activity of either XNk.x2.3 or XNk.x2.5 alone is blocked
in Xenopus embryos, the heart is mildly affected. However, heart formation is abolished when both Nk.x2.3 and Nk.x2.5 gene activities are
blocked (Fu et al. 1998; Grow and Krieg 1998).
As shown by normal Nk.x2.5 expression in some non-cardiogenic
regions of many species, and the inability of overexpression to cause
complete myogenesis, Nk.x2.5 is insufficient to cause cardiomyocyte
differentiation. One important component may be the persistence past a
certain time of development. In Drosophila, of the many tinman-expressing mesoderm cells, it is only cells which maintain tinman gene
activity which adopt the cardiac fate (Frasch 1995). The expression of
dpp in the adjacent ectoderm is required for maintaining tinman gene
expression. Disruption of dpp activity abolishes tinman gene expression
in the cardioblasts, and therefore abolishes heart formation (Frasch
1995). Unlike other vertebrates studied to date, in the zebrafish, the
Nk.x2.5 expression pattern corresponds to the position of cardiogenic
precursors as early as the onset of gastrulation (Chen and Fishman
1996). At the somitogenesis stage, the Nk.x2.5 expression is restricted to
the lateral plate (Fig. 1). At the time as the bilateral cardiac primordia
fuse at the midline, the lateral mesodermal cells posterior to the notochord turn off Nk.x2.5 expression. As fate-mapped by a laser-based
technique, these cells do not populate the heart. Only the lateral
mesodermal cells anterior to the notochord maintain Nk.x2.5 gene activity and populate the heart (Serbedzija et al. 1998).
Classic embryological experiments showed that at early developmental stages, the embryos can compensate for the loss of organ primordia
(Copenhaver 1924). In the zebrafish, the ability to compensate for loss
of cardiac precursors continues until the heart fuses at the midline
(Serbedzija et al. 1998). Interestingly, the cells transiently expressing
Nk.x2.5 adjacent to the notochord do not appear to contribute to this
regulatory compensation (Serbedzija et al. 1998). Together with the fate
mapping analysis, this implies that the notochord has a negative effect
on heart development. In fact, after the ablation of the tip of the notochord, the adjacent, normally non-cardiac Nk.x2.5 cells do develop the
ability to populate the heart (Goldstein and Fishman 1998).
How does the notochord regulate heart formation? One possibility is
through regulating Nk.x2.5 gene activity via the BMP pathway. In the
notochord-ablated zebrafish embryos, the Nk.x2.5 expression domain