Planar cell polarity: intracellular asymmetry and supracellular gradients of Frizzled.

Planar cell polarity (PCP), the coordinated orientation of structures such as cilia, mammalian hairs or insect bristles, depends on at least two molecular systems. We have argued that these two systems use similar mechanisms; each depending on a supracellular gradient of concentration that spans a field of cells. In a linked paper, we studied the Dachsous/Fat system.

Planar cell polarity: intracellular asymmetry and supracellular gradients of Dachsous.

The slope of a supracellular molecular gradient has long been thought to orient and coordinate planar cell polarity (PCP). Here we demonstrate and measure that gradient. Dachsous (Ds) is a conserved and elemental molecule of PCP; Ds forms intercellular bridges with another cadherin molecule, Fat (Ft), an interaction modulated by the Golgi protein Four-jointed (Fj).

Planar cell polarity in the larval epidermis of and the role of microtubules.

We investigate planar cell polarity (PCP) in the larval epidermis. The intricate pattern of denticles depends on only one system of PCP, the Dachsous/Fat system. Dachsous molecules in one cell bind to Fat molecules in a neighbour cell to make intercellular bridges.

A refutation to 'A new A-P compartment boundary and organizer in holometabolous insect wings'.

We respond to a recent report by Abbasi and Marcus who present two main findings: first they argue that there is an organiser and a compartment boundary within the posterior compartment of the butterfly wing. Second, they present evidence for a previously undiscovered lineage boundary near wing vein 5 in Drosophila, a boundary that delineates a "far posterior" compartment. Clones of cells were marked with the yellow mutation and they reported that these clones always fail to cross a line close to vein 5 on the Drosophila wing.

Planar cell polarity: two genetic systems use one mechanism to read gradients.

Our aim in this short Primer is to explain the principles of planar cell polarity (PCP) in animal development. The literature in this small field is complex and specialized, but we have extracted a simple and central story from it. We explain our hypothesis that polarity, initially cued by the direction of slope of a multicellular gradient, is interpreted at the cellular level so that each cell becomes molecularly polarised.

Planar cell polarity: the gene acts independently on both the Ds/Ft and the Stan/Fz systems.

Epithelial cells are polarised within the plane of the epithelium, forming oriented structures that have a coordinated and consistent polarity (planar cell polarity, PCP). In , at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the 'core' or Starry night/Frizzled system. Here, we study the gene and its protein products Prickle and Spiny leg.

Francis Crick: A Singular Approach to Scientific Discovery.

Francis' office window (at the Salk) commanded a panorama of the Pacific. "This grand natural scene was a physical correlate of Francis's intellectual world: wide-ranging, brilliantly lit, a little overawing, but also immensely inviting and above all an exciting place to be." (Mitchison, 2004).

The Last 50 Years: Mismeasurement and Mismanagement Are Impeding Scientific Research.

In the last 50 years, there have been many changes to the substance, conduct, and style of research. Many of these changes have proved disastrous to the life of scientists and to science itself. As a consequence, the near-romantic spirit of adventure and exploration that inspired young scientists of my own and earlier generations has become tarnished.

Planar cell polarity: the Dachsous/Fat system contributes differently to the embryonic and larval stages of Drosophila.

The epidermal patterns of all three larval instars (L1-L3) ofDrosophilaare made by one unchanging set of cells. The seven rows of cuticular denticles of all larval stages are consistently planar polarised, some pointing forwards, others backwards. In L1 all the predenticles originate at the back of the cells but, in L2 and L3, they form at the front or the back of the cell depending on the polarity of the forthcoming denticles.

Regions within a single epidermal cell of Drosophila can be planar polarised independently.

Planar cell polarity (PCP), the coordinated and consistent orientation of cells in the plane of epithelial sheets, is a fundamental and conserved property of animals and plants. Up to now, the smallest unit expressing PCP has been considered to be an entire single cell. We report that, in the larval epidermis of Drosophila, different subdomains of one cell can have opposite polarities.

Plasticity of both planar cell polarity and cell identity during the development of Drosophila.

Drosophila has helped us understand the genetic mechanisms of pattern formation. Particularly useful have been those organs in which different cell identities and polarities are displayed cell by cell in the cuticle and epidermis (Lawrence, 1992; Bejsovec and Wieschaus, 1993; Freeman, 1997). Here we use the pattern of larval denticles and muscle attachments and ask how this pattern is maintained and renewed over the larval moult cycles.

The mechanisms of planar cell polarity, growth and the Hippo pathway: some known unknowns.

Planar cell polarity (PCP) is a small but important area of research. In this review we discuss a limited number of topics within the PCP field, chosen because they are difficult, unsolved, controversial or just because we find them interesting. Because Drosophila is the best studied and technically most amenable system we have concentrated on it, but also consider some examples from work on vertebrates.

Substrate-borne vibratory communication during courtship in Drosophila melanogaster.

Courtship in Drosophila melanogaster has become an iconic example of an innate and interactive series of behaviors. The female signals her acceptance of copulation by becoming immobile in response to a male's display of stereotyped actions. The male and female communicate via vision, air-borne sounds, and pheromones, but what triggers the female's immobility is undetermined.

Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity.

Many epithelia have a common planar cell polarity (PCP), as exemplified by the consistent orientation of hairs on mammalian skin and insect cuticle. One conserved system of PCP depends on Starry night (Stan, also called Flamingo), an atypical cadherin that forms homodimeric bridges between adjacent cells. Stan acts together with other transmembrane proteins, most notably Frizzled (Fz) and Van Gogh (Vang, also called Strabismus).

The muscle pattern of the Drosophila abdomen depends on a subdivision of the anterior compartment of each segment.

In the past, segments were defined by landmarks such as muscle attachments, notably by Snodgrass, the king of insect anatomists. Here, we show how an objective definition of a segment, based on developmental compartments, can help explain the dorsal abdomen of adult Drosophila. The anterior (A) compartment of each segment is subdivided into two domains of cells, each responding differently to Hedgehog.

Planar cell polarity: fashioning solutions.

Scientists like to consider themselves as especially objective, but, however hard we try we cannot be very different from everyone else. Like them we helplessly absorb our knowledge, our perspectives, our valuation of whether something is exciting or boring from those around us. In this "extra view" I reflect on fashion, illustrating by a small discovery of ours, and discussing why it was not made before.

Planar cell polarity: the orientation of larval denticles in Drosophila appears to depend on gradients of Dachsous and Fat.

The larval ventral belts of Drosophila consist of six to seven rows of denticles that are oriented, some pointing forwards, some backwards. We present evidence that denticle orientation is determined almost entirely by Dachsous and Fat, one of two planar cell polarity systems. If we change the distribution of Dachsous we can alter the polarity of denticles.

Mechanosensilla in the adult abdomen of Drosophila: engrailed and slit help to corral the peripheral sensory axons into segmental bundles.

The abdomen of adult Drosophila bears mechanosensory bristles with axons that connect directly to the CNS, each hemisegment contributing a separate nerve bundle. Here, we alter the amount of Engrailed protein and manipulate the Hedgehog signalling pathway in clones of cells to study their effects on nerve pathfinding within the peripheral nervous system. We find that high levels of Engrailed make the epidermal cells inhospitable to bristle neurons; sensory axons that are too near these cells are either deflected or fail to extend properly or at all.

Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for fat.

The Drosophila genes fat (ft) and dachsous (ds) encode large atypical cadherins that collaborate to coordinately polarize cells in the plane of the epithelium (planar cell polarity) and to affect growth via the Warts/Hippo pathway. Ft and Ds form heterodimeric bridges that convey polarity information from cell to cell. four-jointed (fj) is a modulator of Ft/Ds activity that acts in a graded fashion in the abdomen, eye, and wing.

Do the protocadherins Fat and Dachsous link up to determine both planar cell polarity and the dimensions of organs?

Most, perhaps all cells in epithelial sheets are polarized in the plane of the sheet. This type of polarity, referred to as planar cell polarity (PCP), can be expressed in the orientation of cilia and stereocilia, in oriented outgrowths such as hairs, in the plane of cell division, in directed cell movement and possibly in the orientation of axon extension. Another popular area in current research is growth: there is an attempt to find systems that fix the shape and size of organs.

Planar cell polarity: A bridge too far?

The mechanisms of planar cell polarity are being revealed by genetic analysis. Recent studies have provided new insights into interactions between three proteins involved in planar cell polarity: Flamingo, Frizzled and Van Gogh.

The abdomen of Drosophila: does planar cell polarity orient the neurons of mechanosensory bristles?

Background: In the adult abdomen of Drosophila, the shafts of mechanosensory bristles point consistently from anterior to posterior. This is an example of planar cell polarity (PCP); some genes responsible for PCP have been identified. Each adult bristle is made by a clone of four cells, including the neuron that innervates it, but little is known as to how far the formation or positions of these cells depends on PCP.