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Proper regulation of cell polarity is essential to normal growth, differentiation and function of all animal tissues. It is easy to recognize that a fibroblast migrating across a petri dish is polarized along two axes; the first relative to the substratum, on which the cell migrates (apical/basal polarity), and the second relative to the direction of migration (the so-called leading and lagging edges). However, it is perhaps not as widely appreciated that most cells within a tissue also exhibit inherent polarity along similar axes. In addition to apical/basal polarity, cells are also frequently polarized along a planar axis, with cells aligning relative to each other and to the epithelial sheet. This coordinated organization is termed planar cell polarity (PCP). In the last several years, it has been found that PCP is essential for polarized cell orientation, division and movement, processes that are essential for normal embryonic development. This issue of Organogenesis focuses on the roles PCP plays in the formation of various organ systems and how this process might affect the disease state.
Planar cell polarity has been recognized and studied in depth in insects for several decades. However, until recently, it was largely ignored in vertebrates. Perhaps one explanation for the chasm in the level of attention paid to this process in different phyla was the availability of simple assays that could function as readouts of the process. In the fly, PCP is easily discernible by the orientation of hair-like projections (bristles) from individual cells on the integument, appendages and wings. In vertebrates, there was no simple readout (in skin, while orientation of hair/fur is ultimately a readout of PCP, the hair follicle is composed of numerous cells working in concert to produce the actual hair, thus complicating understanding of the mechanism.). However, this is changing, as over the last several years, forward and reverse genetic studies have begun to reveal numerous roles for PCP in vertebrate development and disease, and the field has been growing at a tremendous rate. Now, it is difficult to find a developing vertebrate organ system in which PCP has not been suggested to play an essential role. In the following reviews, the reader will find several articles discussing the role of PCP in various cellular contexts.
The first review, written by Saw Myat Thands Maung and Andreas Jenny, provides an excellent overview of PCP focusing on the fly model system. This article introduces the concept of PCP and all of the conserved molecular regulators involved. It serves as a great first read for those just entering the field or as an excellent update of recent advances. Each of the subsequent articles focuses on the role of PCP in the development or maintenance of specific vertebrate organ systems.
The second review, by Tom Carroll and Amrita Das, focuses on the role of PCP in establishment of tubule diameter in the metanephric kidney. Recent findings suggest that perturbation of PCP may play a causal role in the development and progression of polycystic kidney disease, one of the most common and lethal genetic disorders found in humans. In addition to outlining the evidence for PCP in regulating tubule diameter, the authors discuss other potential roles for this process in kidney development and disease. Finally, they propose the intriguing concept that the stromal fibroblasts may provide directional information during PCP establishment.
The third review, by Yuki Sugiyama, Frank Lovicu and John McAvoy, provides a detailed overview of mammalian lens development, with an emphasis on potential roles for PCP in this process. The lens is a relatively simple tissue, composed of only two cell types (epithelia and fiber cells), that represents one of the clearest examples of planar polarity in vertebrates. Although still in a relatively early phase of investgation, there is excellent evidence that PCP controls directional cell movements and cell orientation in this system. The precise molecular and cellular processes controlling these events are still unclear; however, they are certain to undergo intense investigation in the near future. The lens shows enormous potential to expand upon our understanding of the causes and effects of PCP in vertebrates and the similarities and differences in the mechanisms between vertebrates and invertebrates.
The fourth review is by Sebatian Dworkin, Stephen Jane and Charbel Darido. Here, the authors focus on the role of PCP in the epidermis. Not only are recent findings on the regulation of PCP during epidermal development covered, they also provide unique insights into the role of PCP during epidermal maintenance and repair. Although studies on the role of PCP in tissue repair/maintenance have, to date, been limited, this area is certain to receive intense focus in the near future. This topic is of particular note given recent data suggesting misregulation of some PCP determinants in human cancers.
The fifth review is by Laura Yates and Charlotte Dean. Like the kidney, the respiratory system represents an essential organ system whose development is regulated by PCP. In their review, Yates and Dean cover the known and speculated roles for PCP during normal development of the lung. They also provide some unique speculation about potential roles for PCP in various respiratory diseases. Although still preliminary, these studies have the potential to significantly impact human health and reveal basic aspects of PCP regulation in human disease.
Finally, the last review, covering the role of PCP during skeletal development, comes from Sarah Romereim and Andrew Dudley. A number of recent studies have found that PCP is required for coordination of cell shape, cell division and cell movement during limb development, all of which serve to assure that the bone undergoes proper morphogenesis and takes on its proper size and shape. Although not as simple a system as the lens, the skeleton is also an extremely powerful system in which to study the role of PCP in normal development and pathobiology.
As is always the case, none of these reviews represents the last word on PCP in any organ system. In fact, the study of PCP in vertebrates is still in its relative infancy. Right now, most of the work focuses on the role of PCP in tissue development. However as the reader will see, there is substantial evidence for the involvement of PCP defects in human diseases, and this evidence is likely to keep growing. Indeed, it is quite remarkable that a basic science field that originally was initiated to study why bristles on an insect all pointed in the same direction now has such potential to directly impact human health. It is an excellent example of why basic research is so valuable and why it is still essential to support it.
These reviews are meant to introduce the readers to the concept of PCP and to provide examples of model systems and cellular processes where PCP plays a crucial role. Hopefully, these reviews will propel interest in, and exploration of, PCP, and the next decade will be as enlightening as the past. One thing is clear, PCP research is headed in the right direction.