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1.
Differentiation of vascular precursor cells
2. Development of arteries, veins and lymphatic
vessels
3. Common molecular control of neural and vascular
development
1.Differentiation
of vascular precursor cells
In
adult humans, bone marrow-derived vascular precursor cells
participate to neovascularisation processes. These precursors
represent interesting targets for gene therapy. Vascular precursors
express the receptor 2 for vascular endothelial growth factor
(VEGF), the major inducer of physiological and pathological
angiogenesis. We have identified vascular precursor cells
in early chick embryos based on the expression of the VEGFR2
(1, 2).
We have recently isolated two signaling molecules specifically
expressed by these precursors which potentially regulate their
differentiation. We are analysing the role of these two molecules
in embryonic and adult vascular precursor cells.
To determine if circulating vascular progenitors are already
produced during embryonic development and what are their developmental
potentialities, we produced quail-chick parabiosis. Using
a specific marker of quail endothelial cells, we showed that
these cells circulated and integrated numerous embryonic organs
but always in a low number. However, these circulating cells
are mobilized in a great number during an experimental angiogenesis.
We are now studying where these circulating endothelial cells
come from and what is the first stage of their emergence in
the embryo.
2.
Development of arteries, veins and lymphatic vessels
We
are studying the role of two growth factor receptors, neuropilin-1
and –2 (NRP-1, NRP-2) during the development of arteries,
veins and lymphatic vessels. These two receptors have been
identified in the nervous system, where they play a role in
axonal guidance. In the vascular system, these receptors act
as co-receptors for members of the VEGF family. In the vascular
system, NRP-1 is selectively expressed in arterial endothelium,
while NRP-2 labels venous and lymphatic endothelial cells
(3, 4).
We are studying specific roles of NRP receptors in these different
vascular compartments using mice carrying deletions of the
NRP-1 and –2 genes. We are also using the chick embryo
model to investigate specific roles of these receptors. Using
the chick embryo, we have recently shown that hemodynamic
forces play an important role during arterio-venous differentiation :
neither arteries nor veins develop in the absence of blood
flow and experimental manipulation of the flow can transform
arteries into veins and vice-versa (5)
(see movie).
3.
Common molecular control of neural and vascular development
The
nervous system and the vascular system show important anatomical
similarities. In addition, several molecules controlling the
development of both systems have been recently identified,
suggesting common control mechanisms in the proliferation
and guidance of vessels and nerves. These molecules include
the NRP receptors, which act on both neural and vascular development.
Moreover, growth factors such as VEGF which were thought to
act specifically during vascular development also play a role
in neuronal survival. We will study the interactions between
the developing vascular and nervous system using transgenic
mice carrying both vascular and neural reporter genes.
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