Biomedical Engineering Reference
In-Depth Information
direction with respect to the body axes, mainly because of difficulties in
identifying a global cue in Drosophila . Instead of a single global cue, recent
reports indicated several local cues as well as mechanical forces during
growth and morphogenesis can polarize core PCP proteins and regulate pla-
nar polarity in Drosophila wing epithelium ( Aigouy et al., 2010; Sagner et al.,
2012 ). In this review, I have highlighted the role of Wnt morphogen in
establishing PCP in vertebrate. Recent progress on this issue has taken us
a step closer to understanding Wnt-initiated PCP establishment.
However, more efforts should be aimed at exploiting the precise
regulatory mechanism of Wnt signal inputs on PCP as we have achieved
in canonical Wnt/ b -catenin signaling pathway. Since it is likely that such
regulation does not occur at transcriptional level in Wnt/PCP pathway, it
has been challenging to devise a relevant and productive assay system to
study PCP in vitro . Another challenge is understanding how the
morphogen gradient instructs asymmetrical distribution of core PCP
proteins. Advanced live imaging techniques will be essential on top of an
in vitro PCP assay system in mammalian cells. Another interesting
question is how PCP is maintained during regeneration. Studies on
proliferating skins gave some clues. Eevenport and her colleagues showed
that in mouse basal epithelia cells, mitotic endocytosis of core PCP
proteins (Flamingo, Frizzled, and Vangl) and selectively recycling back to
the cell surface (Frizzled to posterior side and Vangl to anterior side) will
reestablish PCP ( Devenport et al., 2011 ). Whether secreted Wnt proteins
have impact on this process is unknown. Probably not, since evidence has
been shown that such process is reliant on neighboring polarized cells
( Devenport et al., 2011 ). Nevertheless, how endocytic vesicles containing
Frizzled or Vangl interpret directional cues from neighboring cells and
recycle selectively remains unknown. Similarly, during initial PCP
establishment in embryonic development, how Wnt morphogen regulates
polarized intracellular trafficking of core PCP proteins is also
unidentified. Answering the above questions will provide much more
mechanistic insight
to our understanding of PCP establishment and
maintenance.
ACKNOWLEDGMENT
The author is supported by the Intramural Research Program of the National Human
Genome Institute of the National Institutes of Health. I thank Dr. Yingzi Yang for
critical discussions in writing this chapter.
Search WWH ::




Custom Search