Biomedical Engineering Reference
In-Depth Information
Nonautonomy is nowmost readily observed using genetic mosaics to exam-
ine polarity in and around a clone of cells missing or overexpressing a PCP
gene of interest. Of the six core proteins, loss-of-function clones of
fz
and
vang
strongly influence the polarity of neighboring nonmutant tissue, re-
ferred to as domineering nonautonomy (
Adler et al., 2000; Casal et al.,
2002; Taylor, Abramova, Charlton, & Adler, 1998; Vinson & Adler,
1987
). These observations clearly indicate that polarity disruption at a
clone boundary can propagate between cells and the influence of these
effects can reach as far as tens of cells away from the clone boundary.
Associated with and underlying the nonautonomy seen in hair polarity
patterns, Fz and Vang have been experimentally shown to recruit each other
to adjacent sides of intercellular junctions in neighboring cells (
Fig. 2.2A
;
A
B
Fz
Vang
Fz
Vang
Fz
Vang
Fz
Vang
Vang
Fz
Vang
Fz
Vang
Fz
C
D
Vang
Fmi (Vang)
Vang
Fz
Fmi
Fmi (Fz)
Fmi
Fz
Figure 2.2 Generation and amplification of asymmetry by the core module. (A) Inter-
cellular signaling. Mutual intercellular recruitment between Fz in one cell and Vang
in the neighboring cell (red arrows) is required for core module function. Initially, Fz
and Vang are distributed uniformly around the adherens junctions but become segre-
gated to proximal and distal sides, as shown. (B) Intracellular signaling. Segregation of
Fz and Vang requires mutual repulsion that requires activity of the cytoplasmic core pro-
teins. The mechanism of this repulsion is not well defined. (C and D) Two models for the
mutual intercellular recruitment between Fz and Vang.
Chen et al. (2008)
(C) propose that
recruitment depends on asymmetric signaling through Flamingo homodimers in which
eachmonomer adopts different functional states. The state associated with Vang (orange)
is the basal state, while the state associated with Fz (red) is induced by interaction with Fz.
No contact between Fz and Vang is required. In contrast, Wu et al. (2008) (D) propose
unidirectional signaling that requires physical interaction between Fz and Vang, while
symmetric Fmi homodimers scaffold the interaction.
