Morphogenesis by Orientated Cell Division - Mechanisms of Morphogenesis - page 295

FIGURE 23.10 Apico-basal orientation systems (green) can orientate the plane of division in the apico-basal
axis but it cannot specify orientation within the plane of the epithelium itself.

Loss of heterozygosity (to an effectively homozygous mutant condition) by clones of cells in
the colon causes them to develop into a disorganized overgrowth of the gut epithelium; this
may later transform to become a carcinoma. Most theories about the aetiology of adematous
polyposis coli concentrate on the ability of the APC protein to inhibit the Wnt signalling
pathway, 26,27 but it is possible that a disorientation of cell division plays a major role in allow-
ing cells to pile up on each other. Indeed, mice heterozygous for an APC mutation do indeed
show defects in spindle orientation in their colon epithelium. 28
There are other proteins that also play a part in orientating the spindle with respect to the
apico-basal axis. To describe them all would be tedious, especially because most seem to
operate essentially the same way, by either excluding or grabbing asters. Apico-basal orien-
tation cannot be the only mechanism for controlling the orientation of division, however,
because it cannot specify polarity within the plane of the epithelium ( Figure 23.10 ).
Orientation of cell division within the plane of an epithelium (and other tissues) is impor-
tant in morphogenesis. It is, for example, one of the driving forces of vertebrate neurulation,
which is described in more detail in Chapter 18; the mitoses in the epithelium on each side of
the neural tube are orientated so that daughter cells are produced towards the longitudinal
axis of the embryo 29 ( Figure 23.11 ).
One system for giving epithelial cells a sense of direction within their plane has been
described in Chapter 16. The membrane at one side of the cell using this system, the end
called 'North' in this topic ) bears the adhesion molecule Flamingo, the transmembrane sig-
nalling molecule Frizzled and its cytoplasmic relay Dishevelled. On the South side, Flamingo
is also present but with Strabisumus ( Vangl) and the cytoplasmic protein Prickled. Each

type of complex antagonizes the presence of the other one, and the presence of North
complex proteins on one cell is stabilized by contact with the South proteins on an adjacent
membrane of a neighbouring cell. More detail, a summary diagram (Figure 16.8) and refer-
ence citations can be found in Chapter 16.
In many systems that involve orientation of mitosis within the epithelial plane, mutation
of the proteins in either the North or the South complexes makes cells divide in random

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) Compass points have been used instead of alignments with embryonic axes so that planar polarization can
be discussed as generally as possible, since different examples of planar polarization align differently with
the body at different times and in different organs.