Epidermal stem cell clusters
in the basal layer of human interfollicular epidermis form clusters
that can be reconstituted in vitro. In order to supply the
interfollicular epidermis with differentiated cells, the size of these
clusters must be controlled. Evidence suggests that control is regulated
via differentiation of stem cells on the periphery of the clusters.
Moreover, there is growing evidence that this regulation is mediated by
signalling pathway. In this work, we developed theoretical arguments,
in conjunction with computer simulations of a model of the basal
layer, to show that regulation of differentiation is the most likely
mechanism for cluster control. In addition, we showed that stem cells
must adhere more strongly to each other than they do to differentiated cells. We also showed that lateral-induction,
mediated by the Notch signalling pathway, is a natural mechanism for
cluster control. It can not only indicate to cells the size of the
they are in and their position within it, but it can also control the
cluster size. This can only be achieved by postulating a secondary,
cluster wide, differentiation signal, and cells with high Delta expression being deaf to this signal.
This work was published in Developmental Biology.
is a common skin disease seen as red scaly patches on the skin,
especially the joints and the scalp. The disease is heritable but not
contagious. It can first appear at any time in a persons life and can
be brought about by any number of factors including adolescence or
stress. The disease can be treated with creams applied to the skin but
it is not curable; the lesions may reappear continuously throughout a
Skin is composed of two layers. The outermost layer is made up of skin
cells including the dead surface cells that slough off. The innermost
layer is made up of fibres and blood vessels. The fibers anchor the
skin's cells to the body and give skin its elasticity. In normal skin
the outermost layer is about 0.1mm thick. In psoriatic skin this layer
is much thicker with a large buildup of dead cells that flake off as
scales. The blood vessels become wider increasing blood flow to the
skin and giving the lesions their red appearence.
The skin is thought to become thicker because some cells grow and
divide more rapidly than normal. This is what we tried to model with
This movie shows the nitrix
oxide (left) and peroxynitrite (right) concentrations in a simulated 2D
section of a developing psoriatic plaque with three capillaries. Black
represents low concentrations and yellow high concentrations. This movie
shows the collagen density in the same plaque. Black represents the
epidermis, blue the basal cells, dark red the capillaries and
red-yellow increasing collagen density.
This work was published in the Journal of Theoretical Biology.
Created 11 April 2007.