The Questions of Developmental Biology

This fusion occurs at about 29 hours in chick development and at 3 weeks in human
gestation (see Figure 15.3C,D). The unfused posterior portions of the endocardium become the
openings of the vitelline veins into the heart. These veins will carry nutrients from the yolk sac
into the sinus venosus. The blood then passes through a valvelike flap into the atrial region of the
heart. Contractions of the truncus arteriosus speed the blood into the aorta.
Pulsations of the heart begin while the paired primordia are still fusing. The pacemaker of
this contraction is the sinus venosus. Contractions begin here, and a wave of muscle contraction is
propagated up the tubular heart. In this way, the heart can pump blood even before its intricate
system of valves has been completed. Heart muscle cells have their own inherent ability to
contract, and isolated heart cells from 7-day rat or chick embryos will continue to beat in petri
dishes (Harary and Farley 1963; DeHaan 1967). In the embryo, these contractions become
regulated by electrical stimuli from the medulla oblongata via the vagus nerve, and by 4 days, the
electrocardiogram of a chick embryo approximates that of an adult.
Looping and formation of heart chambers
In 3-day chick embryos and 5-
week human embryos, the heart is a
two-chambered tube, with one atrium
and one ventricle (Figure 15.5). In the
chick embryo, the unaided eye can see
the remarkable cycle of blood entering
the lower chamber and being pumped
out through the aorta. The looping of the
heart converts the original anteriorposterior
polarity of the heart tube into
the right-left polarity seen in the adult (Figures 15.5 and 15.6). Thus,
the portion of the heart tube destined to become the right ventricle
lies anterior to the portion that will become the left ventricle. This
looping is dependent upon the left-right patterning proteins (Nodal,
Lefty-2) discussed in Chapter11. Within the heart primordium,
Nkx2 5 regulates the Hand1 and Hand2 transcription factors. Although
the Hand proteins appear to be synthesized throughout the early heart
tube, Hand1 becomes restricted to the future left ventricle, and Hand2 to
the right, as looping commences. Without these proteins, looping fails to
occur normally and the ventricles fail to form properly (Srivastava et al.
1995; Biben and Harvey 1997).
The Pitx-2 transcription factor, activated solely in the left side of
the lateral plate mesoderm, is also critical for proper heart looping, and it
may regulate the expression of proteins such as the extracellular matrix
protein flectin to regulate the physical tension of the heart tissues on the
different sides (Figure 15.7; Tsuda et al. 1996). Transcription factors Nkx2-5 and MEF2C also
activate the Xin gene, whose protein product, Xin (Chinese for "heart"), may mediate the
cytoskeletal changes essential for heart looping (Wang et al. 1999).
The separation of atrium from ventricle is specified by the several transcription factors
that become restricted to either the anterior or the posterior portion of the heart tube (see Figure
15.6; Bao et al. 1999; Bruneau et al. 1999; Wang et al. 1999). The partitioning of this tube into a
distinctive atrium and ventricle is accomplished when cells from the myocardium produce a
factor (probably transforming growth factor β3) that causes cells from the adjacent endocardium