|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
|
Fig. 7. The averaging model. (A) Imagine a gradient of Fz activity from 1000
downwards (see top diagram, upper row). A cell takes into account both its
position, given to it by the scalar of an X gradient, but also the scalars of
its neighbours. After five iterations (lower row) the gradient does not change
(see supplementary material). (B) However, now introduce a
fz– clone of five cells across with an activity
level of 0. At the edge of a clone, a cell (say, at level 930) now finds
itself between a fz– cell (with level 0) and its
normal neighbour (level 920). After the same five iterations (lower row), the
values of several of the fz+ cells have changed and,
consequently, the scalars, the vectors and the polarity as shown. Red
indicates a cell whose polarity has been reversed (a=0.75, see
supplementary material). (C) A simple but speculative model of the functional
interactions. This model is based on our results and helps explain them. Using
Stan, each cell compares the Fz activity of adjoining cells, forming hairs
that point towards the neighbour with the lowest activity. The top row shows
the normal epithelium, with an activity gradient of Fz (increased activities
are indicated by larger fonts). The cadherin Stan bridges from cell to cell
and activates Vang. This activation is repressed by Fz activity. Within the
cell, Vang, a membrane protein, represses Fz. Consider any three consecutive
cells. High Fz activity in cell 1 inhibits Stan in the same cell, an effect
which passes across the Stan-Stan bridge to repress Stan in cell 2, thus
reducing Vang activation and increasing Fz activity in cell 2. This effect on
Fz activity is counterbalanced by cell 3, which has itself lower Fz activity
and hence higher Stan activity; this propagates back, via the Stan-Stan
bridge, to enhance Stan activity on the opposite surface of cell 2, thus
enhancing Vang activation and reducing Fz activity in cell 2. The whole field
is subject to the X gradient which limits the tendency of Fz activity to rise.
The effects of stan–, fz–
and Vang– clones are shown in the bottom three
rows.
|
