Biomedical Engineering Reference
In-Depth Information
therefore may regulate cell polarity signaling during gastrulation (
Seifert,
Ibrahim, Stodtmeister, Winklbauer, & Niessen, 2009
). I would like to
propose that the growth cone filopodia can be viewed as “mobile
adherens junction” searching for the missing half and can respond to
many cues (
Fig. 6.5B
).
The cell polarity signaling pathways offer an opportunity to understand
signaling mechanisms for growth cone steering. Because of the intimate in-
teractions of A-BP and PCP signaling, it is likely that one may depend on the
other. For example, one possibility is that A-BP specifies the proximal-distal
axis of the growth cone and PCP components may polarize growth cones
perpendicular to the proximal-distal axis (
Fig. 6.5B
). An alternative to this
model is that PCP and A-BP are not organized along these perpendicular
axes in growth cones but rather may function in collaboration to amplify
each other's signaling level in certain selected filopodia, causing a massive
turning signal.
Because A-BP and PCP components are expressed in all neurons and
these signaling components can regulate actin, microtubule and membrane
trafficking, a spontaneous question is whether this mechanism, or “growth
cone compass,” is universal. Is there any evidence that other axon guidance
signaling system than the Wnt system can also access this “compass?” The
following findings are beginning to provide encouraging clues:
1
. Par3, Par6, and aPKC are required for axon outgrowth-promoting
effects of Netrin-1 and NGF, and Par3 and Par6 are required for ventrally
directed growth cone commissural axons to the rat spinal cord midline
(
Hengst et al., 2009
). This study suggests that Netrin-1 can access this
potentially universal machinery via A-BP components (
Fig. 6.5C
).
2
. PTK7 is a newly identified Wnt coreceptor in PCP signaling (
Peradziryi
et al., 2012
). Its
Drosophila
orthologue, OTK, forms a complex with
machinery. aPKC/Par3/Par6 is required for Netrin-1-stimulated axon outgrowth (
Hengst,
Deglincerti, Kim, Jeon, & Jaffrey, 2009
). PTK7, a Wnt coreceptor in PCP signaling is a cor-
eceptor for PlexinA1, which mediates semaphorin signaling (
Peradziryi, Tolwinski, &
Borchers, 2012; Toyofuku et al., 2004; Wagner, Peradziryi, Wehner, & Borchers, 2010
).
N-Cadherin, a potent stimulator for axon out growth, is found in the adherens
junction of chick cardiac muscle cells and lens epithelial cells. Slit
-
Robo can inhibit
adhesion by both E-cadherins and N-cadherins and regulate retinal neurite
outgrowth, adhesion, or retinal ganglion cell apical process retraction (
Rhee, Buchan,
Zukerberg, Lilien, & Balsamo, 2007; Rhee et al., 2002; Santiago-Martinez, Soplop,
Patel, & Kramer, 2008; Wong, Baudet, Norden, Leung, & Harris, 2012
).
