Genetic Dissection of Heart Development
115
proper looping is dependent on factors in addition to laterality decisions,
for example, proper cardiac function. Therefore, it is difficult to interpret the cause of mutant phenotypes. Interestingly, in the zebrafish,
12 hours before looping, the arterial end of the heart transiently moves
to the left side of the embryo. This process is referred to as cardiac
jogging (Fig. 1) (Chen et al. 1997). Although jogging has not been
described in other vertebrates, it may not be a zebrafish-specific feature.
In fact, the mouse embryonic heart also shifts to the left prior to looping
(En Li and Richard Harvey, personal communication). Jogging appears
to be solely affected by laterality decisions, therefore, it is a more
reliable indicator for cardiac laterality. Using both jogging and looping
as morphological assays for left-right patterning, 279 mutations from
the Tiibingen zebrafish stock center were screened and 21 were found to
have cardiac laterality defects (Chen et al. 1997).
These mutations confirm BMP4 as a mediator between the embryonic left-right signals and the cardiac laterality. Normally, BMP4 expression is left-predominant in the heart soon after the bilateral primordia fuse at the midline. This asymmetric pattern is randomized in the
mutant embryos with an abnormal jog. A left-predominant BMP4 expression correlates with a left-jog. Right-predominant BMP4 expression
correlates with a right-jog. A symmetric BMP4 expression pattern correlates with randomized jogging (Chen et al. 1997).
These mutants also reveal jogging as a reliable indicator for embryonic laterality. The direction of jogging reflects the preceding BMP4
asymmetry and is predictive of the direction of the subsequent looping.
In both wild-type and mutant embryos, a left-jogged heart always loops
to the right. A right-jogged heart always loops to the left. If the heart
fails to jog and stays at the midline, the subsequent looping is randomized, and could be to the right or to the left, or the heart remains
unlooped (Chen et al. 1997).
The cardiac laterality screen was based on the existing collection of
zebrafish mutants. Therefore, all the cardiac laterality mutants identified
in this screen bear additional defects. Based on the phenotypes, these
mutants can be categorized into three classes: those with dorsoventral
defects, those with midline defect, and those with a curved body shape
(Chen et al. 1997). This supports the notion that the proper patterning of
the left-right axis is dependent on the proper patterning of the dorsoventral axis and the midline structures (Danos and Yost 1995; Danos and
115
proper looping is dependent on factors in addition to laterality decisions,
for example, proper cardiac function. Therefore, it is difficult to interpret the cause of mutant phenotypes. Interestingly, in the zebrafish,
12 hours before looping, the arterial end of the heart transiently moves
to the left side of the embryo. This process is referred to as cardiac
jogging (Fig. 1) (Chen et al. 1997). Although jogging has not been
described in other vertebrates, it may not be a zebrafish-specific feature.
In fact, the mouse embryonic heart also shifts to the left prior to looping
(En Li and Richard Harvey, personal communication). Jogging appears
to be solely affected by laterality decisions, therefore, it is a more
reliable indicator for cardiac laterality. Using both jogging and looping
as morphological assays for left-right patterning, 279 mutations from
the Tiibingen zebrafish stock center were screened and 21 were found to
have cardiac laterality defects (Chen et al. 1997).
These mutations confirm BMP4 as a mediator between the embryonic left-right signals and the cardiac laterality. Normally, BMP4 expression is left-predominant in the heart soon after the bilateral primordia fuse at the midline. This asymmetric pattern is randomized in the
mutant embryos with an abnormal jog. A left-predominant BMP4 expression correlates with a left-jog. Right-predominant BMP4 expression
correlates with a right-jog. A symmetric BMP4 expression pattern correlates with randomized jogging (Chen et al. 1997).
These mutants also reveal jogging as a reliable indicator for embryonic laterality. The direction of jogging reflects the preceding BMP4
asymmetry and is predictive of the direction of the subsequent looping.
In both wild-type and mutant embryos, a left-jogged heart always loops
to the right. A right-jogged heart always loops to the left. If the heart
fails to jog and stays at the midline, the subsequent looping is randomized, and could be to the right or to the left, or the heart remains
unlooped (Chen et al. 1997).
The cardiac laterality screen was based on the existing collection of
zebrafish mutants. Therefore, all the cardiac laterality mutants identified
in this screen bear additional defects. Based on the phenotypes, these
mutants can be categorized into three classes: those with dorsoventral
defects, those with midline defect, and those with a curved body shape
(Chen et al. 1997). This supports the notion that the proper patterning of
the left-right axis is dependent on the proper patterning of the dorsoventral axis and the midline structures (Danos and Yost 1995; Danos and