Biomedical Engineering Reference
In-Depth Information
1. INTRODUCTION
Although it is well known that most cells show polarity along an api-
cal/basal (A/B) axis, it has become increasingly evident that cells are also po-
larized along a second axis perpendicular to the A/B axis. This is easy to
visualize for migrating cells as the leading and lagging edges. However, even
epithelial cells can show this second axis of polarity, and when all or most of
the cells within the tissue coordinate their polarity in one direction, it is re-
ferred to as tissue or planar cell polarity (PCP).
Although intensively studied in the fly for many years, PCP was largely
ignored by vertebrate biologists. However, over the past 10 years, mutagen-
esis of vertebrate orthologs of genes necessary for PCP establishment in flies
has revealed multiple requirements during normal development and tissue
maintenance. In some tissues, the connection between the PCP genes
and the actual PCP is clear, while in others, they are a complete mystery.
In this review, we characterize a number of processes that are thought to
be regulated by PCP during kidney development and maintenance. We re-
view what is known about the molecular regulators and the cellular pro-
cesses controlled.
2. PLANAR CELL POLARITY
PCP describes polarity within the plane of a tissue, perpendicular to the
apical-basal polarity of the cells. It can manifest itself externally, for example,
in the directional alignment of Drosophila wing hairs and cuticular bristles (all
point in the same direction), the orientation of mammalian body hair, or the
orientation of stereociliary bundles of the inner ear. Less readily identifiable
but essential examples are the organization of the ommatidia of the Drosophila
eye or the uniform cellular orientation, coordinated directional cell migration,
and oriented cell division that drive tissue morphogenesis. It is important to
emphasize that mere asymmetry alone is not equivalent to PCP. Individual
cells can show asymmetry, but if that asymmetry is not coordinated between
all (or most) cells within a tissue, it is not PCP.
2.1. The Fat/Dachsous pathway
Mutagenesis screens in Drosophila have identified a number of genes nec-
essary for establishing PCP in all or most tissues. These genes are broken up
into distinct pathways based on where and when they act and also their
