Cell Signaling During Primitive Hematopoiesis
443
3.2
Ectoderm
Numerous lines of evidence point to an es-
sential role of ectodermally derived signals
in
Xenopus
primitive erythroid develop-
ment. Similar to the mouse and chick,
gastrulation movements in
Xenopus
em-
bryos bring the prospective hematopoietic
tissue into close contact with a different
germ layer, the ectoderm. Isolated and
cultured prospective ventral mesoderm
(posterior ventral blood island precur-
sors) from early gastrula stage embryos
develop ‘‘blood-like cells’’ that are not
hemoglobinized and do not express globin
protein. However, coculture of the ventral
mesoderm fragments with fragments of
prospective ectoderm from stage-matched
embryos leads to robust differentiation
of primitive erythrocytes. Disruption of
BMP signaling in the prospective dorsal
or ventral ectoderm signiFcantly reduces
the number of circulating primitive ery-
throcytes in animals without affecting
D/V patterning. Importantly, in embryos
in which BMP signaling is disrupted in
the prospective ectoderm, speciFcation of
hematopoietic cells, as evidenced by
scl
expression, appears to occur normally.
Moreover, normal production of erythroid
progenitors occurs, as evidenced by wild
type levels of
gata1
at early stages of ven-
tral blood island development. However,
at subsequent developmental stages,
gata1
expression is not maintained,
globin
ex-
pression is absent or signiFcantly reduced,
and the number of circulating primi-
tive erythrocytes is severely decreased. In
other words, blocking the ability of ecto-
dermal cells to respond to BMPs leads
to defects in primitive erythroid differ-
entiation, whereas the speciFcation of
primitive erythroid progenitors appears
to occur normally. These results strongly
suggest that BMP signaling in the ecto-
derm induces the production of a sec-
ondary signal that acts on the prospective
hematopoietic tissue to support the sur-
vival of primitive erythrocytes. It has been
proposed that this secondary signal is a
BMP because blocking production of bi-
ologically active BMP2, 4, and 7 in the
prospective ventral ectoderm also inhibits
primitive erythrocyte development, and
BMPs positively regulate their own ex-
pression. Thus, in theory, inhibiting BMP
signaling in the prospective ectoderm
could abrogate expression of endogenous
BMPs that signal to the hematopoietic
mesoderm. Because BMP expression is
normally extinguished in the prospective
dorsal ectoderm during gastrulation, and
inhibiting BMP signaling in the prospec-
tive dorsal ectoderm is sufFcient to block
primitive erythrocyte differentiation, the
secondary signal generated by the ecto-
derm that signals to the hematopoietic
progenitors is most likely to include a
cytokine or cytokines other than or in ad-
dition to BMPs.
3.3
Endothelial Cells
Endothelial cells differentiate in close
physical association with primitive hema-
topoietic cells in all vertebrate species
and some evidence suggests that en-
dothelial
cells
support
the
differenti-
ation
of
the
primitive
erythroid
lin-
eage.
In
the
zebraFsh,
for
example,
transplantation of wild type cells into
cloche mutants showed that in the mu-
tant environment, wild type cells do
not maintain
gata1
expression. Given
that the cloche mutation also leads to
the absence of endothelial cells, it has
been
suggested
that
the
noncell
au-
tonomous effects on
gata1
maintenance
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