Blood, 1 March 2003, Vol. 101, No. 5, pp. 1665-1665
Bringing blood to life
Since ancient times, the heart and blood have been inextricably
linked as fundamental elements to the process of life. William Harvey
was the first to provide a plausible mechanism for blood circulation
when in 1628 he defined the circulatory system to comprise a
cardiac pump, intact vascular system, and recirculating blood. Harvey
believed that blood was the fountain of life, the first (tissue) to
live, and the last to die. His thesis has been supported in part by
modern evidence that murine embryos mutant for genes necessary for
blood, endothelial, and/or cardiac development who fail to establish or
maintain circulation perish in utero. Harvey never articulated when he
believed the blood comes to "life" (circulation commences)
during mammalian development. Emergence of primitive erythroblasts
(PEs) and nascent endothelial cells on embryonic day (E) 7.0 in
the murine yolk sac may herald the beginnings of a circulatory system.
But beating of the developing heart tube and linkage of the yolk sac
and embryonic vascular systems on E8.25 is identified by some as
evidence for the onset of systemic blood flow. But is blood
flow equivalent to circulation? When does circulation (as defined by
Harvey) begin in the murine embryo?
McGrath and colleagues (page 1669) provide compelling evidence that
circulation is established in a graded series of maturational steps.
Using simple tools and clever intuition, they examined murine embryos
from E8.0 to E10.5 to determine the steady state density of PEs in the
embryo proper and the distribution of PEs in the developing embryonic
vessels. They report that the first PEs enter embryonic vessels at the
4 somite pair (sp) stage of development (E8.25) but that complete
equilibration of PEs in the circulation is not accomplished until 35 sp
(E10.5). What takes so long? The authors suggest that the process of
cardiac maturation and/or vascular remodeling may regulate the
dispersal of PEs throughout the vasculature. William Harvey would be intrigued.
Mervin C. Yoder, Jr
Indiana University School of
Medicine
