The Questions of Developmental Biology

However, diffusion of nutrients can take place only when blood flows slowly and has
access to cell membranes. So here is a paradox: the constraints of diffusion mandate that vessels
be small, while the laws of hydraulics mandate that vessels be large. Living organisms have
solved this paradox by evolving circulatory systems with a hierarchy of vessel sizes (LaBarbera
1990). This hierarchy is formed very early in development (and is already well established in the
3-day chick embryo). In dogs, blood in the large vessels (aorta and vena cava) flows over 100
times faster than it does in the capillaries. With a system of large vessels specialized for transport
and small vessels specialized for diffusion (where the blood spends most of its time), nutrients
and oxygen can reach the individual cells of the growing organism.
But this is not the entire story. If fluid under constant pressure moves directly from a
large-diameter tube into a small-diameter tube (as in a hose nozzle), the fluid velocity increases.
The evolutionary solution to this problem was the emergence of many smaller vessels branching
out from a larger one, making the collective cross-sectional area of all the smaller vessels greater
than that of the larger vessel. Circulatory systems show a relationship (known as Murray's law) in
which the cube of the radius of the parent vessel approximates the sum of the cubes of the radii of
the smaller vessels. The construction of any circulation system must negotiate among all of these
physical, physiological, and evolutionary constraints.
Vasculogenesis: formation of blood vessels from blood islands
Blood vessel formation is intimately connected to blood cell formation. Indeed, blood
vessels and blood cells are believed to share a common precursor, the hemangioblast (Figure
15.14). Not only do blood vessels and blood cells share common sites of origin, but mutations of
certain transcription factors in mice and zebrafish will delete both blood cells and blood vessels.
In addition, the earliest blood cells and the earliest capillary cells share many of the same rare
proteins on their cell surfaces (Wood et al. 1997; Choi et al. 1998; Liao and Zon 1999).
Blood vessels are constructed by two processes: vasculogenesis and angiogenesis (Figure
15.15). During vasculogenesis, blood vessels are created de novo from the lateral plate
mesoderm. In the first phase of vasculogenesis, groups of splanchnic mesoderm cells are
specified to become hemangioblasts, the precursors of both the blood cells and the blood vessels
(Shalaby et al. 1997). These cells condense into aggregations that are often called blood islands.
The inner cells of these blood islands become hematopoietic stem cells (the precursors of all the
blood cells), while the outer cells become angioblasts, the precursors of the blood vessels. In the
second phase of vasculogenesis, the angioblasts multiply and differentiate into endothelial cells,
which form the lining of the blood vessels. In the third phase, the endothelial cells form tubes and
connect to form the primary capillary plexus, a network of capillaries. In the second process,
angiogenesis, this primary network will be remodeled and pruned into a distinct capillary bed,
arteries, and veins (Risau 1997; Hanahan 1997). It is important to realize that the capillary