Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1236 Chapter 22: Stem Cells and Tissue Renewal
Less obvious than the blood vessels are the lymphatic vessels. These carry no
blood and have much thinner and more permeable walls than the blood vessels.
They provide a drainage system for the fluid (lymph) that seeps out of the blood
vessels, as well as an exit route for white blood cells that have migrated from blood
vessels into the tissues. Less happily, they can also provide the path by which
cancer cells escape from a primary tumor to invade other tissues. The lymphatics
form a branching system of tributaries, all ultimately discharging into a single
large lymphatic vessel, the thoracic duct, which opens into a large vein close to the
heart. Like blood vessels, lymphatics are lined with endothelial cells.
Thus, endothelial cells line the entire blood and lymphatic vascular system,
from the heart to the smallest capillary, and they control the passage of materials—and
the transit of white blood cells—into and out of the bloodstream. Arteries,
veins, capillaries, and lymphatics all develop from small vessels constructed
primarily of endothelial cells and a basal lamina: connective tissue and smooth
muscle are added later where required, under the influence of signals from the
endothelial cells.
Endothelial Tip Cells Pioneer Angiogenesis
To understand how the vascular system comes into being and how it adapts to the
changing needs of tissues, we have to understand endothelial cells. How do they
become so widely distributed, and how do they form channels that connect in just
the right way for blood to circulate through the tissues and for lymph to drain back
to the bloodstream?
Endothelial cells originate at specific sites in the early embryo from precursors
that also give rise to blood cells. From these sites, the early embryonic endothelial
cells migrate, proliferate, and differentiate to form the first rudiments of blood
vessels—a process called vasculogenesis. Subsequent growth and branching of
the vessels throughout the body occurs mainly by proliferation and movement of
the endothelial cells of these first vessels, in a process called angiogenesis.
Angiogenesis occurs in a broadly similar way in the young organism as it grows
and in the adult during tissue repair and remodeling. We can watch the behavior
of the cells in naturally transparent structures, such as the cornea of the eye or the
fin of a tadpole, or in tissue culture, or in the embryo. The embryonic retina, which
blood vessels invade according to a predictable timetable, provides a convenient
example for experimental study. Each new vessel originates as a capillary sprout
from the side of an existing capillary or small venule (Figure 22–24). At the tip
of the sprout, leading the way, is an endothelial cell with a distinctive character.
This tip cell has a pattern of gene expression somewhat different from that of the
endothelial stalk cells following behind it, and while they divide, it does not. The
tip cell’s most striking feature is that it puts out many long filopodia, resembling
pericytes clinging
to outer face of
small blood vessel
10 µm
Figure 22–23 Pericytes. The scanning
electron micrograph shows pericytes
wrapping their processes around a small
blood vessel (a post-capillary venule) in the
mammary gland of a cat. Pericytes are also
present around capillaries, but are much
more sparsely distributed there. (From
T. Fujiwara and Y. Uehara, Am. J. Anat.
170:39–54, MBoC6 1984. With m23.32/22.23 permission from
Wiley-Liss.)
red blood cell endothelial cell capillary lumen
(A)
new capillary branch
pseudopodial processes
guide the development
of the capillary sprout
capillary sprout
hollows out to
form tube
tip cell
Figure 22–24 Angiogenesis. (A) A new blood capillary forms by the sprouting of an endothelial
cell from the wall of an existing small vessel. An endothelial tip cell, with many filopodia, leads the
advance of each capillary sprout. The endothelial stalk cells trailing behind the tip cell become
hollowed out to form a lumen. (B) Blood capillaries sprouting in the retina of an embryonic mouse
that had a red dye injected into the bloodstream, revealing the capillary lumen opening up behind
the tip cell (Movie 22.2). (B, from H. Gerhardt et al., J. Cell Biol. 161:1163–1177, 2003. With
permission from the author.)
(B)
20 µm