The Questions of Developmental Biology

the developmental fates of the stem cells' progeny. These investigators placed plugs of bone
marrow in a spleen and then injected stem cells into it. Those CFU-S cells that came to reside in
the spleen formed colonies that were predominantly erythroid, whereas those colonies that
formed in the marrow were predominantly granulocytic. In fact, colonies that straddled the
borders of the two tissue types were predominantly erythroid in the spleen and granulocytic in the
marrow. Such regions of determination are referred to as hematopoietic inductive
microenvironments (HIMs). In early blood cell formation (in the mesoderm surrounding the
mammalian yolk sac), the endothelial cells of the blood islands appear to be heterogeneous HIMs,
inducing the stem cells to form different blood and lymphocyte lineages (Lu et al. 1996;
Auerbach et al. 1997).
Sites of hematopoiesis
Vertebrate blood development occurs in two phases: a transient embryonic ("primitive")
phase of hematopoiesis is followed by the definitive ("adult") phase. These phases differ in their
sites of blood cell production, the timing of hematopoiesis, the morphology of the cells produced,
and even the type of globin genes used in the red blood cells. The embryonic phase of
hematopoiesis is probably used to initiate the circulation that provides the embryo with its initial
blood cells and with its capillary network to the yolk. The definitive phase of hematopoiesis is
used to generate more cell types and to provide the stem cells that will last for the lifetime of the
individual.
Embryonic hematopoiesis is associated with the blood islands in the ventral mesoderm
near the yolk. In the mouse, embryonic erythropoiesis is seen in the blood islands in the
mesoderm surrounding the yolk sac. In chick embryos, the first blood cells are seen in those
blood islands forming in the posterior marginal zone near the site of hypoblast initiation (Wilt
1974; Azar and Eyal-Giladi 1979). In Xenopus, the ventral mesoderm forms a large blood island
that is the first site of hematopoiesis. Zebrafish are the exceptions to this pattern, as their first
blood cells form in the paraxial mesoderm. However, this region of paraxial mesoderm contains
the same hematopoietic transcription factors as the ventral mesoderm in Xenopus, mice, and fish
(Detrich et al. 1995). Since vertebrate ventral mesoderm is associated with high concentrations of
BMPs, it is not surprising that ectopic BMP 2 and 4 can induce blood and blood vessel formation
in Xenopus, and that interference with BMP signaling prevents blood formation (Maeno et al.
1994; Hemmati-Brivanlou and Thomsen 1995). Moreover, in the zebrafish, the swirl mutation,
which prevents BMP2 signaling, also abolishes ventral mesoderm and blood cell production
(Mullins et al. 1996).
The embryonic hematopoietic
cell population, however, is transitory.
The hematopoietic stem cells that last
the lifetime of the organism are derived
from the mesodermal area surrounding
the aorta. This was shown in the chick
by a series of elegant experiments by
Dieterlen-Lièvre, who grafted the
blastoderm of chickens onto the yolk of
Japanese quail (Figure 15.23).