3+ 4/2002 - Společnost pro pojivové tkáně

DEVELOPMENT OF SKELETAL
PATTERN IN VERTEBRATE LIMBS
C TICKLE
Division of Cell and Developmental Biology,Wellcome
Trust Biocentre, University of Dundee, Dow Street,
Dundee DD15EH, UK
Vertebrate limb development is a reiterative
process that culminates in the formation
of a complex organ with precisely
arranged cells and tissues. The first step is
essentially part of establishing the main
body plan and results in formation of limb
buds at the proper places in the embryo;
the next step is an autonomous process in
which cell-cell interactions within the limb
bud result in formation of tissue primordia;
and the final step is the subsequent morphogenesis
of these primordia to give final
anatomy. We will focus on experimental
analysis of the skeletal development of digits
in chick embryos. A model for mechanisms
that specify number and type of digit
skeletal primordia will be outlined with
suggested roles for Sonic hedgehog and
Bone Morphogenetic Proteins. Recent
work on subsequent morphogenesis of the
digit skeleton in chick embryos will be
described with special reference to the role
of Fibroblast Growth Factor signalling in
determining phalange number and specifying
the tip.
GENETIC AND CELLULAR CONTROL
OF SKELETAL DEVELOPMENT
AND HOMEOSTASIS
Bjorn R. Olsen
Department of Cell Biology, Harvard Medical School
and Department of Oral and Developmental Biology,
Harvard School of Dental Medicine, Boston, MA, USA
Most of the bones in the vertebrate
skeleton develop by the process of endo-
110
LOCOMOTOR SYSTEM vol. 9, 2002, No. 3+4
chondral ossification: Condensing mesenchymal
cells differentiate into chondrocytes
which produce cartilage models of
the future bones, and these models are subsequently
replaced by bone marrow and
bone in a series of steps involving chondrocyte
hypertrophy and invasion of blood
vessels, osteoclastic (chondroclastic) cells
and osteoblastic progenitors from the perichondrium
into cartilage. This is followed
by differentiation, proliferation and bone
matrix production by osteoblasts and
remodelling of the bone through the coupled
activities of osteoclasts and
osteoblasts. Recent studies have provided
exciting new insights into some of the
genetic and molecular regulatory steps in
these processes.
VEGFA and its receptors VEGFR1 and
VEGFR2 have multiple roles during endochondral
ossification. First, VEGF is
expressed by mesenchymal cells around
cartilage models before chondrocyte hypertrophy
is initiated within the models, and
this expression appears to stimulate angiogenesis
into the perichondrial regions.
Second, as chondrocyte hypertrophy
occurs within the cartilage models,VEGF is
expressed by hypertrophic chondrocytes
(controlled by the transcription factor
Cbfal/Runx2) and is essential for the
chemotactic migration of osteoclasts (chondroclasts)
and endothelial cell sprouts into
the cartilage. Finally, VEGF has a direct
effect on osteoblasts and stimulates their
production of mineralized matrix.
VEGF is therefore both an indirect
(through stimulation of angiogenesis) and
a direct stimulator of bone formation. For
example, addition of a soluble VEGF receptor
to the medium of mouse calvarial
explant cultures completely suppresses the
thickening of the bone seen in control cul-