Biomedical Engineering Reference
In-Depth Information
Wnt5 expressed at higher levels in posterior commissure ( Yoshikawa et al.,
2003 )( Fig. 6.1B ). Derailed is a Wnt binding receptor, which mediates
axon repulsion by Wnt5a concentrated in the posterior commissure. Since
then, a number of publications reported the role of Wnt signaling in axon
guidance in a variety of neuronal types (corticospinal motor neurons,
retinal ganglion cells, olfactory sensory neurons, dorsal root ganglion cells,
dopaminergic, and serotonergic neurons) ( Bl ly t l, ;
Domanitskaya et al., 2010; Fenstermaker et al., 2010; Hilliard &
Bargmann, 2006; Hutchins, Li, & Kalil, 2011; Keeble et al., 2006;
Kennerdell, Fetter, & Bargmann, 2009; Li, Hutchins, & Kalil, 2009; Liu
et al., 2005; Lu, Yamamoto, Ortega, & Baltimore, 2004; Pan et al., 2006;
Prasad & Clark, 2006; Rodriguez-Gil & Greer, 2008; Sato, Umetsu,
Murakami, Yasugi, & Tabata, 2006; Schmitt et al., 2006; Shimizu et al.,
2011; Song et al., 2010 ). Because morphogens are known for their role in
specifying cell types by activating different transcription programs at
different concentrations, their function in axon guidance had not been
anticipated. This has also led to the investigation on how Wnt family
morphogens signal in growth cones to guide axons ( Zou, 2004 ).
In an earlier review in 2004, it was cautiously postulated that “PCP
signaling pathway,” a “variation of PCP signaling pathway,” or a “subset
of PCP machinery” might be involved in Wnt-mediated axon guidance.
The caution was motivated by the fact that only Frizzled3 had been shown
to mediate axon guidance at that time ( Zou, 2004 ). In 2005, another PCP
component, Ceslr3, showed similar function to Frizzled3 in axon guidance
( Tissir, Bar, Jossin, De Backer, & Goffinet, 2005 ). However, Flamingo, the
Drosophila homologue of the Celsrs, has additional function independent of
PCP signaling ( Berger-Muller & Suzuki, 2011 ). Therefore, the evidence of
PCP signaling in axon guidance was still preliminary.
In more recent years, new work has begun to reveal that cell polarity
signaling components may play a central role in Wnt-mediated axon guid-
ance. In 2008, components of A-BP signaling, atypical PKC/Par3/Par6
complex, were first shown to directly mediate Wnt attraction and anterior
turning of spinal cord commissural axons ( Wolf et al., 2008 ). In 2010 and
2011, multiple PCP components, Frizzled3, Ceslr3, and Vangl2, were di-
rectly tested and found to be required in anterior-posterior guidance of
brainstem serotonergic and dopaminergic axons and the spinal cord com-
missural axons ( Fenstermaker et al., 2010; Shafer et al., 2011 )( Fig. 6.1A
and B ). In addition, Vangl2 was found localized on tips of extending
filopodia and promoted commissural axon growth in response to Wnt5a
Search WWH ::




Custom Search