Biomedical Engineering Reference
In-Depth Information
Bastock et al., 2003; Collier & Gubb, 1997; Collier et al., 2005; Feiguin
et al., 2001; Krasnow & Adler, 1994; Park et al., 1996; Strutt, 2001;
Strutt & Warrington, 2008; Usui et al., 1999; Yan et al., 2008
). The basis
for the domineering nonautonomy has been studied at length. Early
studies established that it was a property of abnormal local signaling
between cells (
Adler, Taylor, et al., 2000
). The current consensus model
is that the intercellular signaling between neighboring cells due to the
asymmetric accumulation of PCP proteins is propagated on a cell-by-cell
basis and this is the basis for the domineering nonautonomy
(
Amonlirdviman et al., 2005; Goodrich & Strutt, 2011; Maung & Jenny,
2011; Tree et al., 2002; Wu & Mlodzik, 2008
). Thus, a cell with no Fz
cannot recruit Vang to the juxtaposed membrane (
Wu & Mlodzik, 2008
).
This leads to a high level of Vang on the side of the cell distal to the
mutant membrane. This would be propagated for a number of cells and
such a system could be at the heart of the intercellular signaling required
for PCP. One drawback to such a model is that the function of a gene
such as
dsh
that acts cell autonomously is required for the antisymmetric
accumulation of other PCP proteins (
Axelrod, 2001; Klingensmith et al.,
1994; Strutt, 2001; Theisen et al., 1994; Tree et al., 2002; Usui et al.,
1999
). At first glance, this result would seem to contradict the asymmetry
propagation model. However, computer simulations indicate that the
model can explain the observations (
Amonlirdviman et al., 2005;
Schamberg, Houston, Monk, & Owen, 2010
) as only modest levels of
asymmetry may be required for signaling and this may be difficult to detect
in immunostaining experiments. There remains, however, a need for an
explanation for the results that indicate the cell nonautonomous function
precedes the cell autonomous function (
Strutt & Strutt, 2002
).
It is worth noting that this mechanismworks well to explain both normal
PCP development and domineering nonautonomy in a tissue where all cells
express the
fz/stan
pathway proteins and show the asymmetric accumula-
tion. In the eye, only the R3 and R4 cells need to express
fz
pathway genes
for the development of normal PCP (
Zheng et al., 1995
). In these cells,
fz/stan
pathway proteins accumulate asymmetrically with proteins that
accumulate on the distal side of wing cells accumulating in the R3 cell mem-
brane that is juxtaposed to the R4 cell (
Strutt et al., 2002
). Similarly, proteins
that accumulate on the proximal side of wing cells accumulate on the R4 cell
membrane that is juxtaposed to R3 (
Strutt et al., 2002
). Thus, heterotypic
interactions across cell membranes seem likely to be a mechanism used in the
generation of the two domains (e.g., see
Wu & Mlodzik, 2008
).
