The Questions of Developmental Biology

The Heart
The circulatory system is one of the great achievements of the lateral plate mesoderm.
Consisting of a heart, blood cells, and an intricate system of blood vessels, the circulatory system
provides nourishment to the developing vertebrate embryo. The circulatory system is the first
functional unit in the developing embryo, and the heart is the first functional organ. The
vertebrate heart arises from two regions of splanchnic mesoderm one on each side of the
body that interact with adjacent tissue to become specified for heart development.
Specification of heart tissue and fusion of heart rudiments
In amniote vertebrates, the embryo is a flattened disc, and the lateral plate mesoderm
does not completely encircle the yolk sac. The presumptive heart cells originate in the early
primitive streak, just posterior to Hensen's node and extending about halfway down its length.
These cells migrate through the streak and form two groups of mesodermal cells lateral to (and at
the same level as) Hensen's node (Figure 15.2; Garcia-Martinez and Schoenwolf 1993). These
groups of cells are called the cardiogenic mesoderm. The cells forming the atrial and ventricular
musculature, the cushion cells of the valves, the Purkinje conducting fibers, and the endothelial
lining of the heart are all generated from these two clusters (Mikawa 1999).
When the chick embryo is only 18 20 hours old, the presumptive heart cells move
anteriorly between the ectoderm and endoderm toward the middle of the embryo, remaining in
close contact with the endodermal surface (Linask and Lash 1986). When these cells reach the
lateral walls of the anterior gut tube, migration ceases. The directionality for this migration
appears to be provided by the foregut endoderm. If the cardiac region endoderm is rotated with
respect to the rest of the embryo, migration of the cardiogenic mesoderm cells is reversed. It is
thought that the endodermal component responsible for this movement is an anterior-to-posterior
concentration gradient of fibronectin. Antibodies against fibronectin stop the migration, while
antibodies against other extracellular matrix components do not (Linask and Lash 1988a,b).
The endoderm and primitive streak also specify the some of the cardiogenic cells to
become heart muscles. Cerberus and an unknown factor, possibly BMP2 in the anterior
endoderm, induce the synthesis of the Nkx2-5 transcription factor in the migrating mesodermal
cells that will become the heart* (Komuro and Izumo 1993; Lints et al. 1993; Sugi and Lough
1994; Schultheiss et al. 1995; Andrée et al. 1998). Nkx2-5 is a critical protein in instructing the
mesoderm to become heart tissue, and it activates the synthesis of other transcription factors
(especially members of the GATA and MEF2 families). Working together, these transcription
factors activate the expression of genes encoding cardiac muscle-specific proteins (such as
cardiac actin, atrial naturetic factor, and the alpha myosin heavy chains).