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J.-N. Chen and M. C. Fishman
extends more posteriorly (Goldstein and Fishman 1998). In Drosophila,
tinman expression in the cardiac progenitors is dependent on dpp activity from the adjacent ectoderm (Frasch 1995). A DNA-binding site of
medea, a downstream responsive gene of dpp, is present in the tinman
promoter and is required for proper tinman gene expression (Xu et al.
1998). The vertebrate homologue of dpp, BMP4, is expressed in the
zebrafish heart and BMP4 antagonists, such as noggin and chordin, are
expressed in the notochord (Bauer et al. 1998), implying that the regulatory circuits of dpp-tinman may be conserved in vertebrates.
7.3 Chamber Formation
A multi-chambered heart is a feature of all vertebrates, but not of
primitive chordates, suggesting that it is a recent evolutionary innovation of vertebrates. It serves to ensure unidirectional flow and high-pressure circulation (Fishman and Chien 1997), in turn permitting significant increase of the size. How chambers becomes demarcated, how the
chamber fates are specified, and how the chamber-specific cell types
differentiate is poorly understood.
The helix-loop-helix gene, dHAND, is the only one known to be
important in chamber formation. It is expressed initially in the cardiogenic region of the developing mouse heart and later restricted to the
right ventricle and some neural crest derivatives (Srivastava et al. 1995;
Srivastava et al. 1997). Targeted gene disruption of dHAND abolishes
the right ventricle (Srivastava et al. 1997). Mutation in dHAND also
abolishes cardiac ventricle formation in the zebrafish embryos (Stainier,
personal communication). Furthermore, a downstream factor of
dHAND, ufdl gene, is deleted in human patients with cardiac and
craniofacial anomalies (Yamagishi et al. 1999). How genes in the
dHAND pathway control cardiac chamber formation is not known, but
evidence suggests that dHAND is required for cardiac cell survival
(Srivastava 1999). Other pathways or genes might be involved in cardiac
chamber formation. Mutant embryos of pandora and lonely atrium do
not have a ventricular structure (Fig. 2) (Chen et al. 1996; Stainier et al.
1996). Molecular cloning of these genes will shed light on their regulation of cardiac chamber formation.
J.-N. Chen and M. C. Fishman
extends more posteriorly (Goldstein and Fishman 1998). In Drosophila,
tinman expression in the cardiac progenitors is dependent on dpp activity from the adjacent ectoderm (Frasch 1995). A DNA-binding site of
medea, a downstream responsive gene of dpp, is present in the tinman
promoter and is required for proper tinman gene expression (Xu et al.
1998). The vertebrate homologue of dpp, BMP4, is expressed in the
zebrafish heart and BMP4 antagonists, such as noggin and chordin, are
expressed in the notochord (Bauer et al. 1998), implying that the regulatory circuits of dpp-tinman may be conserved in vertebrates.
7.3 Chamber Formation
A multi-chambered heart is a feature of all vertebrates, but not of
primitive chordates, suggesting that it is a recent evolutionary innovation of vertebrates. It serves to ensure unidirectional flow and high-pressure circulation (Fishman and Chien 1997), in turn permitting significant increase of the size. How chambers becomes demarcated, how the
chamber fates are specified, and how the chamber-specific cell types
differentiate is poorly understood.
The helix-loop-helix gene, dHAND, is the only one known to be
important in chamber formation. It is expressed initially in the cardiogenic region of the developing mouse heart and later restricted to the
right ventricle and some neural crest derivatives (Srivastava et al. 1995;
Srivastava et al. 1997). Targeted gene disruption of dHAND abolishes
the right ventricle (Srivastava et al. 1997). Mutation in dHAND also
abolishes cardiac ventricle formation in the zebrafish embryos (Stainier,
personal communication). Furthermore, a downstream factor of
dHAND, ufdl gene, is deleted in human patients with cardiac and
craniofacial anomalies (Yamagishi et al. 1999). How genes in the
dHAND pathway control cardiac chamber formation is not known, but
evidence suggests that dHAND is required for cardiac cell survival
(Srivastava 1999). Other pathways or genes might be involved in cardiac
chamber formation. Mutant embryos of pandora and lonely atrium do
not have a ventricular structure (Fig. 2) (Chen et al. 1996; Stainier et al.
1996). Molecular cloning of these genes will shed light on their regulation of cardiac chamber formation.