Genomes and Genes
Gene Symbol: fj
Alias: CG10917, Dmel\CG10917, four-jointed, CG10917-PA, fj-PA, four jointed
Species: fruit fly
- Willecke M, Hamaratoglu F, Kango Singh M, Udan R, Chen C, Tao C, et al. The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size. Curr Biol. 2006;16:2090-100 pubmed..In contrast, Fat is not required for Merlin localization, and Fat and Merlin act in parallel in growth regulation. Taken together, our data identify a cell-surface molecule that may act as a receptor of the Hippo signaling pathway. ..
- Buckles G, Rauskolb C, Villano J, Katz F. Four-jointed interacts with dachs, abelson and enabled and feeds back onto the Notch pathway to affect growth and segmentation in the Drosophila leg. Development. 2001;128:3533-42 pubmed..Thus, four-jointed may bridge the gap between the signals that direct morphogenesis and those that carry it out. ..
- Strutt D. Organ shape: controlling oriented cell division. Curr Biol. 2005;15:R758-9 pubmed..One mechanism by which organisms control the shape of growing organs is by regulating the orientation of cell divisions. This occurs in the Drosophila wing under the control of genes previously implicated in regulating cell polarity. ..
- Simon M. Planar cell polarity in the Drosophila eye is directed by graded Four-jointed and Dachsous expression. Development. 2004;131:6175-84 pubmed..the establishment of graded expression of the cadherin Dachsous (Ds) and the Golgi-associated protein Four-jointed (Fj)...
- Villano J, Katz F. four-jointed is required for intermediate growth in the proximal-distal axis in Drosophila. Development. 1995;121:2767-77 pubmed..Mutants in the Drosophila four-jointed (fj) gene show reduced growth and altered differentiation only within restricted sectors of the proximal-distal (PD) ..
- Ishikawa H, Takeuchi H, Haltiwanger R, Irvine K. Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains. Science. 2008;321:401-4 pubmed publisher..Our results indicate that Four-jointed regulates Fat signaling by phosphorylating cadherin domains of Fat and Dachsous as they transit through the Golgi. ..
- Bray S. Planar polarity: out of joint?. Curr Biol. 2000;10:R155-8 pubmed..This planar polarity requires the transmembrane receptor Frizzled. Recent studies have shed new light on mechanisms that could be involved in generating or transducing the polarity signal. ..
- Cho E, Feng Y, Rauskolb C, Maitra S, Fehon R, Irvine K. Delineation of a Fat tumor suppressor pathway. Nat Genet. 2006;38:1142-50 pubmed..melanogaster tumor suppressors, establish a basic framework for Fat signaling from receptor to transcription factor and implicate Warts as an integrator of multiple growth control signals. ..
- Brittle A, Repiso A, Casal J, Lawrence P, Strutt D. Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for fat. Curr Biol. 2010;20:803-10 pubmed publisher..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...
- Hogan J, Valentine M, Cox C, Doyle K, Collier S. Two frizzled planar cell polarity signals in the Drosophila wing are differentially organized by the Fat/Dachsous pathway. PLoS Genet. 2011;7:e1001305 pubmed publisher..6) Altering the timing of ds knockdown during wing development can separate the role of the Ft/Ds pathway in wing morphogenesis from its role in Early Fz PCP signaling...
- Matakatsu H, Blair S. Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous. Development. 2012;139:1498-508 pubmed publisher..We also found that the extracellular domain of Ft can act independently of the Ft ICD in PCP and can trigger dominant-negative and boundary effects on Hippo activity, probably via binding to the protocadherin Dachsous. ..
- Zecca M, Struhl G. A feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to Drosophila wing growth. PLoS Biol. 2010;8:e1000386 pubmed publisher..We posit that Wg propels wing growth at least in part by fueling a wave front of Ft-Ds signaling that propagates vg expression from one cell to the next. ..
- Casal J, Lawrence P, Struhl G. Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity. Development. 2006;133:4561-72 pubmed..We consider how polarity may be propagated by Ds-Ft heterodimers acting as bridges between cells. ..
- Cho E, Irvine K. Action of fat, four-jointed, dachsous and dachs in distal-to-proximal wing signaling. Development. 2004;131:4489-500 pubmed
- Strutt H, Mundy J, Hofstra K, Strutt D. Cleavage and secretion is not required for Four-jointed function in Drosophila patterning. Development. 2004;131:881-90 pubmedFour-jointed (fj) is required for proximodistal growth and planar polarity in Drosophila tissues...
- Bosveld F, Bonnet I, Guirao B, Tlili S, Wang Z, Petitalot A, et al. Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway. Science. 2012;336:724-7 pubmed publisher..Our results establish how tissue planar polarization coordinates the local changes of cell mechanical properties to control tissue morphogenesis. ..
- Rogulja D, Rauskolb C, Irvine K. Morphogen control of wing growth through the Fat signaling pathway. Dev Cell. 2008;15:309-21 pubmed publisher..These observations identify Fat as a signaling pathway that links the morphogen-mediated establishment of gradients of positional values across developing organs to the regulation of organ growth. ..
- Matakatsu H, Blair S. Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development. 2004;131:3785-94 pubmed..Nor are distal PCP defects increased by the loss of spatial information from the distally expressed four-jointed (fj) gene, which encodes putative modulator of Ft-Ds signaling...
- Strutt H, Strutt D. Long-range coordination of planar polarity in Drosophila. Bioessays. 2005;27:1218-27 pubmed..Subsequently, this long-range polarity signal is refined by local cell-cell interactions involving the transmembrane molecules Frizzled, Strabismus and Flamingo. The role of these factors in coordinating polarity will be discussed. ..
- Sopko R, Silva E, Clayton L, Gardano L, Barrios Rodiles M, Wrana J, et al. Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown. Curr Biol. 2009;19:1112-7 pubmed publisher..We propose that Ds regulates Dco-dependent phosphorylation of Fat and Fat-associated proteins to control Fat signaling in growth and PCP. ..
- Grzeschik N, Parsons L, Allott M, Harvey K, Richardson H. Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol. 2010;20:573-81 pubmed publisher..Thus, our study implicates Lgl, aPKC, and Crumbs as regulators of tissue growth via the SWH pathway. ..
- Simon M, Xu A, Ishikawa H, Irvine K. Modulation of fat:dachsous binding by the cadherin domain kinase four-jointed. Curr Biol. 2010;20:811-7 pubmed publisher..Fat is regulated by the cadherin Dachsous (Ds) and the protein kinase Four-jointed (Fj), which are expressed in gradients in many tissues...
- Zeidler M, Perrimon N, Strutt D. The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification. Curr Biol. 1999;9:1363-72 pubmed..Interestingly, it appears to act redundantly with unknown factors in this process, providing an explanation for the previous failure to identify a second signal. ..
- Fanto M, Clayton L, Meredith J, Hardiman K, Charroux B, Kerridge S, et al. The tumor-suppressor and cell adhesion molecule Fat controls planar polarity via physical interactions with Atrophin, a transcriptional co-repressor. Development. 2003;130:763-74 pubmed
- Amonlirdviman K, Khare N, Tree D, Chen W, Axelrod J, Tomlin C. Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science. 2005;307:423-6 pubmed..The sufficiency of this model and the experimental validation of model predictions reveal how specific protein-protein interactions produce autonomy or domineering nonautonomy. ..
- Ma D, Yang C, McNeill H, Simon M, Axelrod J. Fidelity in planar cell polarity signalling. Nature. 2003;421:543-7 pubmed..Subsequent action of the Frizzled feedback loop is sufficient to align all the cells cooperatively. This economical system is therefore highly robust, and produces virtually error-free arrays. ..
- Yang C, Axelrod J, Simon M. Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye. Cell. 2002;108:675-88 pubmed
- Neto Silva R, de Beco S, Johnston L. Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Dev Cell. 2010;19:507-20 pubmed publisher..We propose that the codependent regulatory relationship functionally coordinates the cellular activities of Yki and Myc and provides a mechanism of growth control that regulates organ size and has broad implications for cancer. ..
- Mao Y, Rauskolb C, Cho E, Hu W, Hayter H, Minihan G, et al. Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila. Development. 2006;133:2539-51 pubmed..Our results implicate Dachs as a crucial downstream component of a Fat signaling pathway that influences growth, affinity and gene expression during development. ..
- Willecke M, Hamaratoglu F, Sansores Garcia L, Tao C, Halder G. Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation. Proc Natl Acad Sci U S A. 2008;105:14897-902 pubmed publisher..growth but also planar cell polarity, for which it interacts with the Dachsous (Ds) Cadherin, and Four-jointed (Fj), a transmembrane kinase that modulates the interaction between Ds and Fat...
- Zeidler M, Perrimon N, Strutt D. Multiple roles for four-jointed in planar polarity and limb patterning. Dev Biol. 2000;228:181-96 pubmed..The subtle phenotypes of mutant flies, and the diverse patterning processes in which it is involved, suggest that four-jointed may act as a modifier of the activity of multiple other signalling factors. ..
- Lawrence P, Struhl G, Casal J. Planar cell polarity: one or two pathways?. Nat Rev Genet. 2007;8:555-63 pubmed..We argue that the prevailing opinion that planar polarity depends on a single genetic pathway is wrong and conclude that there are (at least) two independently acting processes. This conclusion has major consequences for the PCP field. ..
- Tang C, Sun Y. Use of mini-white as a reporter gene to screen for GAL4 insertions with spatially restricted expression pattern in the developing eye in drosophila. Genesis. 2002;34:39-45 pubmed
- Ambegaonkar A, Pan G, Mani M, Feng Y, Irvine K. Propagation of Dachsous-Fat planar cell polarity. Curr Biol. 2012;22:1302-8 pubmed publisher..is regulated by the graded expression of the Fat ligand Dachsous (Ds) and the cadherin-domain kinase Four-jointed (Fj). The vectors of these gradients influence PCP, whereas their slope can influence growth...
- Strutt H, Strutt D. Planar polarity: photoreceptors on a high fat diet. Curr Biol. 2002;12:R384-5 pubmed..Differential activity of Frizzled in the R3/R4 photo-receptors of Drosophila regulates the orientation of ommatidia. New evidence suggests that the cadherins Dachsous and Fat act upstream of Frizzled in this process. ..
- Hazelwood L, Hancock J. Functional modelling of planar cell polarity: an approach for identifying molecular function. BMC Dev Biol. 2013;13:20 pubmed publisher..The predictions from the model allow direct assignment of functional roles of genes from genetic mosaic analysis of Drosophila wings. ..
- Casal J, Struhl G, Lawrence P. Developmental compartments and planar polarity in Drosophila. Curr Biol. 2002;12:1189-98 pubmed..Here, we present evidence that cell polarity in the abdomen depends on at least two protein gradients (Fj and Ds), each of which is reflected at compartment borders...
- Brittle A, Thomas C, Strutt D. Planar polarity specification through asymmetric subcellular localization of Fat and Dachsous. Curr Biol. 2012;22:907-14 pubmed publisherTwo pathways regulate planar polarity: the core proteins and the Fat-Dachsous-Four-jointed (Ft-Ds-Fj) system. Morphogens specify complementary expression patterns of Ds and Fj that potentially act as polarizing cues...
- GonzÃ¡lez Morales N, GÃ©minard C, Lebreton G, Cerezo D, Coutelis J, Noselli S. The Atypical Cadherin Dachsous Controls Left-Right Asymmetry in Drosophila. Dev Cell. 2015;33:675-89 pubmed publisher..These results identify a direct functional coupling between the LR determinant MyoID and PCP, essential for non-autonomous propagation of early LR asymmetry. ..
- Shao W, Wu J, Chen J, Lee D, Tishkina A, Harris T. A modifier screen for Bazooka/PAR-3 interacting genes in the Drosophila embryo epithelium. PLoS ONE. 2010;5:e9938 pubmed publisher..For 13 of the 17 genes, this is the first report of a link to baz or the regulation of epithelial structure. ..
- Aerts S, Vilain S, Hu S, Tranchevent L, Barriot R, Yan J, et al. Integrating computational biology and forward genetics in Drosophila. PLoS Genet. 2009;5:e1000351 pubmed publisher..A systems genetics approach that combines the power of computational predictions with in vivo genetic screens strongly enhances the process of gene function and gene-gene association discovery. ..
- Galic M, Matis M. Polarized trafficking provides spatial cues for planar cell polarization within a tissue. Bioessays. 2015;37:678-86 pubmed publisher..In this review, we discuss recent findings on the molecular mechanism that links "global" directional signals with local coordinated polarity. ..
- Parkhurst S, Delidakis C. Fly developments: an introspective. Bioessays. 2003;25:87-9 pubmed
- Lim J, Norga K, Chen Z, Choi K. Control of planar cell polarity by interaction of DWnt4 and four-jointed. Genesis. 2005;42:150-61 pubmed..margins is insufficient to induce ommatidial polarity but becomes inductive when coexpressed with Four-jointed (Fj)...
- Herz H, Madden L, Chen Z, Bolduc C, Buff E, Gupta R, et al. The H3K27me3 demethylase dUTX is a suppressor of Notch- and Rb-dependent tumors in Drosophila. Mol Cell Biol. 2010;30:2485-97 pubmed publisher..In summary, these data suggest that dUTX is a suppressor of Notch- and Rbf-dependent tumors in Drosophila melanogaster and may provide a model for UTX-dependent tumorigenesis in humans. ..
- Tsai Y, Sun Y. Long-range effect of upd, a ligand for Jak/STAT pathway, on cell cycle in Drosophila eye development. Genesis. 2004;39:141-53 pubmed..Consistent with the long-range effect, we found that the extracellular Upd protein can be detected over a comparable long range, suggesting that Upd acts directly over a long distance as a signaling molecule. ..
- Gutierrez Aviño F, Ferres Marco D, Dominguez M. The position and function of the Notch-mediated eye growth organizer: the roles of JAK/STAT and four-jointed. EMBO Rep. 2009;10:1051-8 pubmed publisher..These findings redefine the process of organizer formation and function, and they identify four-jointed as a regulatory node, integrating multiple growth-control pathways. ..
- Milton C, Grusche F, Degoutin J, Yu E, Dai Q, Lai E, et al. The Hippo pathway regulates hematopoiesis in Drosophila melanogaster. Curr Biol. 2014;24:2673-80 pubmed publisher..Further, Yorkie or Scalloped hyperactivation induced ectopic crystal cells in a non-cell-autonomous and Notch-pathway-dependent fashion. ..
- Qing Y, Yin F, Wang W, Zheng Y, Guo P, Schozer F, et al. The Hippo effector Yorkie activates transcription by interacting with a histone methyltransferase complex through Ncoa6. elife. 2014;3: pubmed publisher..These findings shed light on Yki-mediated transcriptional regulation and uncover a potential link between chromatin modification and tissue growth. ..
- Muñoz Soriano V, Belacortu Y, Paricio N. Planar cell polarity signaling in collective cell movements during morphogenesis and disease. Curr Genomics. 2012;13:609-22 pubmed publisher..Therefore, new discoveries about the contribution of this pathway to collective cell movements could provide new potential diagnostic and therapeutic targets for these disorders. ..
- Fausti F, Di Agostino S, Sacconi A, Strano S, Blandino G. Hippo and rassf1a Pathways: A Growing Affair. Mol Biol Int. 2012;2012:307628 pubmed publisher..Recently, the impact of RASSF proteins on Hippo signaling potentiating its proapoptotic activity has been addressed, thus, providing further evidence for Hippo's key role in mammalian tumorigenesis as well as other important diseases. ..
- Ishikawa H, Xu A, Ogura E, Manning G, Irvine K. The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins. PLoS ONE. 2012;7:e42988 pubmed publisher..Our results identify FAM20C as a kinase for secreted phosphoproteins and establish a biochemical basis for Raine syndrome. ..
- Kwon H, Waghmare I, Verghese S, Singh A, Singh A, Kango Singh M. Drosophila C-terminal Src kinase regulates growth via the Hippo signaling pathway. Dev Biol. 2015;397:67-76 pubmed publisher..Furthermore, dCsk requires Yki for its growth regulatory functions, suggesting that dCsk is another upstream member of the network of genes that interact to regulate Wts and its effector Yki in the Hippo signaling pathway. ..
- Jolly M, Rizvi M, Kumar A, Sinha P. Mathematical modeling of sub-cellular asymmetry of fat-dachsous heterodimer for generation of planar cell polarity. PLoS ONE. 2014;9:e97641 pubmed publisher..to be generated by complex sets of interactions amongst three proteins - Fat (Ft), Dachsous (Ds) and Four-jointed (Fj). Ft and Ds are two atypical cadherins, which are phosphorylated by Fj, a Golgi kinase...
- Lawlor K, Ly D, Dinardo S. Drosophila Dachsous and Fat polarize actin-based protrusions over a restricted domain of the embryonic denticle field. Dev Biol. 2013;383:285-94 pubmed publisher..Ectopic Ds signaling provides evidence for a model whereby Ds acts to asymmetrically enrich Fat in a neighboring cell, in turn polarizing the cell to specify the position of the actin-based protrusions at the cell cortex. ..
- Carvajal Gonzalez J, Mlodzik M. Mechanisms of planar cell polarity establishment in Drosophila. F1000Prime Rep. 2014;6:98 pubmed publisher..Here, we discuss the current models based on Drosophila studies and incorporate recent insights into this long-standing cell and developmental biology problem. ..
- ..Together, these findings are shedding light on how global cues integrate with local cell interactions to organize cellular polarity at the tissue level. ..
- Postlethwait J, Schneiderman H. Developmental genetics of Drosophila imaginal discs. Annu Rev Genet. 1973;7:381-433 pubmed
- Luo H, Dearolf C. The JAK/STAT pathway and Drosophila development. Bioessays. 2001;23:1138-47 pubmed..Hence, the JAK/STAT pathway in Drosophila serves as an attractive model for in vivo functional analyses of JAK/STAT signaling. ..
- Lawrence P, Casal J. The mechanisms of planar cell polarity, growth and the Hippo pathway: some known unknowns. Dev Biol. 2013;377:1-8 pubmed publisher..We offer some new ways of making sense of published results, particularly those relating to the Frizzled/Starry night and Dachsous/Fat systems of PCP. ..
- Couso J, Bishop S. Proximo-distal development in the legs of Drosophila. Int J Dev Biol. 1998;42:345-52 pubmed..The data suggest a process of regionalization and progressive subdivision of an anlage similar to both insect embryonic segmentation and vertebrate somitogenesis. ..
- Strutt D. Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development. 2003;130:4501-13 pubmed..This review discusses recent findings regarding non-canonical Frizzled signalling and cell polarisation. ..
- Rodrigues A, Zoranovic T, Ayala Camargo A, Grewal S, Reyes Robles T, Krasny M, et al. Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis. Development. 2012;139:4051-61 pubmed publisher..As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine. ..
- Bossuyt W, Chen C, Chen Q, Sudol M, McNeill H, Pan D, et al. An evolutionary shift in the regulation of the Hippo pathway between mice and flies. Oncogene. 2014;33:1218-28 pubmed publisher..We conclude that fundamental differences exist in the upstream regulatory mechanisms of Hippo signaling between Drosophila and vertebrates. ..
- Donoughe S, Dinardo S. dachsous and frizzled contribute separately to planar polarity in the Drosophila ventral epidermis. Development. 2011;138:2751-9 pubmed publisher..Furthermore, we find that the requirement for the Ds system changes as field size increases. Lastly, we find that Ds and its putative receptor Fat (Ft) are enriched in distinct patterns in the epithelium during embryonic development. ..
- Schwank G, Tauriello G, Yagi R, Kranz E, Koumoutsakos P, Basler K. Antagonistic growth regulation by Dpp and Fat drives uniform cell proliferation. Dev Cell. 2011;20:123-30 pubmed publisher..Together, our results indicate that the activities of both signaling pathways are regulated in a parallel rather than sequential manner and that uniform proliferation is achieved by their complementary action on growth. ..
- Okumura M, Sakuma C, Miura M, Chihara T. Linking cell surface receptors to microtubules: tubulin folding cofactor D mediates Dscam functions during neuronal morphogenesis. J Neurosci. 2015;35:1979-90 pubmed publisher..Genetic analyses revealed that TBCD cooperates with Dscam in vivo. Our study may offer new insights into the molecular mechanism underlying the altered neural networks in cognitive disabilities of Down syndrome. ..
- Sing A, Tsatskis Y, Fabian L, Hester I, Rosenfeld R, Serricchio M, et al. The atypical cadherin fat directly regulates mitochondrial function and metabolic state. Cell. 2014;158:1293-1308 pubmed publisher..Defects in mitochondrial activity in ft mutants are independent of Hippo and PCP signaling and are reminiscent of the Warburg effect. ..
- Kölzer S, Fuss B, Hoch M, Klein T. Defective proventriculus is required for pattern formation along the proximodistal axis, cell proliferation and formation of veins in the Drosophila wing. Development. 2003;130:4135-47 pubmed..The study of the regulation of dve expression provides information about the strategies employed to subdivide and pattern the PD axis, and reveals the importance of vg during this process. ..
- Peifer M, McEwen D. The ballet of morphogenesis: unveiling the hidden choreographers. Cell. 2002;109:271-4 pubmed..Several recent papers reveal new insights into the mechanisms by which cells turn their perceptions about fate into action, focusing on the role of Wnt signal transduction in cell polarization and migration. ..
- Kerszberg M, Wolpert L. Specifying positional information in the embryo: looking beyond morphogens. Cell. 2007;130:205-9 pubmed..It is now becoming clear that additional or alternative mechanisms involving interactions among cells are also crucial for positional specification. ..
- Le Garrec J, Kerszberg M. Modeling polarity buildup and cell fate decision in the fly eye: insight into the connection between the PCP and Notch pathways. Dev Genes Evol. 2008;218:413-26 pubmed publisher..The model provides insight into the crosstalk between the PCP and Notch modules in development and illustrates the ability of signaling modules to robustly maintain vital phenotypes in a noisy environment. ..
- Faucheux M, Netter S, Bloyer S, Moussa M, Boissonneau E, Lemeunier F, et al. Advantages of a P-element construct containing MtnA sequences for the identification of patterning and cell determination genes in Drosophila melanogaster. Mol Genet Genomics. 2001;265:14-22 pubmed..Taken together, these results indicate that P[MTW] allows the tagging of patterning and cell determination genes, and thus provides a useful tool for identifying new developmental functions. ..