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RESEARCH HIGHLIGHTS
TISSUE MORPHOLOGY
Branching out
DOI:
10.1038/nrc2023
URLs
EGF
http://www.ncbi.nlm.nih.gov/
entrez/query.fcgi?db=gene&c
md=Retrieve&dopt=full_
report&list_uids=1950
HGF
http://www.ncbi.nlm.nih.gov/
entrez/query.fcgi?db=gene&c
md=Retrieve&dopt=full_
report&list_uids=3082
TGFβ
http://www.ncbi.nlm.nih.gov/
entrez/query.fcgi?db=gene&c
md=Retrieve&dopt=full_
report&list_uids=7040
Breast cancer
http://www.cancer.gov/
cancertopics/types/breast
Many organs in the body are
made up of a network of branched
tubules. Disruption of this network
is evident in human breast cancer,
indicating that the cells are no longer
responsive to positional signals that
govern when and where branches
are formed. Although many of the
global signals that control branching
morphogenesis are known, how these
are integrated at the local (cellular)
level is not clear.
Celeste Nelson, Mina Bissell and
colleagues have investigated whether
the physical position of cells within
a tubule determines their capacity to
form a branch. The authors used collagen gel and different tubule-shaped
molds to predetermine the size and
shape of the tubule. The authors then
seeded these with mouse mammary
epithelial cells and allowed them to
form tubules. The addition of either
epidermal growth factor (EGF) or
hepatocyte growth factor (HGF) was
used to induce branch formation.
The position of the branches was
monitored by staining the nuclei and
collecting many stacked fluorescence
images.
The authors found that branches
occurred only at the ends of the
tubules, and in these regions the
cells underwent epithelial–mesenchymal transition before branching
occurred. On the basis of tubule
geometry and computer modelling,
it is probable that branching is suppressed by the secretion of an inhibitory factor produced by the epithelial
cells. Only at tubule ends or on the
convex side of a curved tubule (see
figure) is the concentration of inhibitor low enough to enable the cells to
respond to the systemic branching
signal produced, in this model, by
EGF or HGF. What is the suppressive factor? Transforming growth
factor-β (TGFβ) is a morphogen that
is known to inhibit branching, and
disruption of TGFβ signalling in the
epithelial cells resulted in branching
from all areas of the tubule. However,
as TGFβ is secreted in an inactive,
latent form, other signals probably
participate in inhibition.
Appreciating how a local cellular
microenvironment can regulate
NATURE REVIEWS | CANCER
cell fate should help us to better
understand the initial changes that
enable tumour cells to invade and
metastasize.
Nicola McCarthy
ORIGINAL RESEARCH PAPER Nelson, C. M.
et al. Tissue geometry determines sites of
mammary branching morphogenesis in
organotypic cultures. Science 314, 298–300
(2006)
Branching tubules (red) are evident on the convex
side and ends of this tubule. Reproduced with
permission from the original research paper ©
(2006) Science.
VOLUME 6 | NOVEMBER 2006
© 2006 Nature Publishing Group