Biomedical Engineering Reference
In-Depth Information
(
Shafer et al., 2011
). The involvement of multiple PCP signaling
components in axon guidance appears to be evolutionarily conserved
because in
Drosophila
, frizzled (fz), strabismus (stbm/Van Gogh), flamingo
(fmi), and disheveled (dsh) are cooperatively required for axonal targeting
and branching of the
Drosophila
mushroom body neurons and Wnt5 was
implicated as the ligand (
Shimizu et al., 2011
)(
Fig. 6.1C
). In the dorsal
cluster neurons,
prickle
,
flamingo
, and
disheveled
promote sensory axon
advance in
Drosophila
(
Mrkusich et al., 2011
)(
Fig. 6.1D
). These recent
studies strongly favor the view that the PCP signaling pathway (and
together with A-BP signaling) may provide a major axon steering
mechanism in response to Wnts.
In each set of published study, a subset of PCP components, three to four
of six, were analyzed. However, if one pools all studies together, five of six
PCP components have been shown required for axon guidance, with the
exception of Diego. Given the conservation of the PCP pathways in other
systems, it is likely that the same set of PCP proteins is involved in axons guid-
ance. Nonetheless, analyses of complete set of “core” PCP genes in each of the
systems will be necessary to conclude whether the entire complement of PCP
pathway is engaged in the growth cones or only a subset of PCP signaling
pathway is sufficient. In addition, analyzing the role of Fat/Dachsous set of
PCP genes in axon guidance will further test the idea how similar the PCP
signaling in growth cone is to other examples of PCP signaling.
3. CAN PCP SIGNALING BE USED IN MOTILE GROWTH
CONES?
PCP is a common structural feature of tissues throughout the animal
kingdom, although most of our knowledge of PCP has been derived from
studies in
Drosophila
(hairs of wing and abdomen, bristles on the surface of
the body, and the ommatidia in the eye) (
Goodrich & Strutt, 2011
). Elegant
fly genetic studies led to the discovery of the key regulatory system, espe-
cially the “core” PCP components that control planar polarity. In more
recent years, orientation of hair follicles in mammalian skins, polarized
stereocilia of inner ear hair cells, and asymmetric position of primary cilia
in the ependymal lining of mammalian brain have emerged as examples
of planar polarity in vertebrates. Strikingly, the same set of “core” PCP com-
ponents controls planar polarity in a highly conserved manner, suggesting
that these “core” components and their robust interactions are part of the
“universal” code for planar polarity. For more complete description of
