Functional modelling of planar cell polarity: an approach for identifying molecular function

BMC Developmental Biology

John M Hancock²  Lee D Hazelwood¹ 

[1] Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK;Department of Physiology, Development & Neuroscience, Cambridge University, Cambridge CB2 3EG, UK

关键词: In-silico phenotyping;    Drosophila;    Self organisation;    Mathematical modelling;    PCP;    Planar polarity;   

Others  :  1085789
DOI  :  10.1186/1471-213X-13-20

 received in 2012-11-28, accepted in 2013-04-30,  发布年份 2013

【 摘 要 】

Background

Cells in some tissues acquire a polarisation in the plane of the tissue in addition to apical-basal polarity. This polarisation is commonly known as planar cell polarity and has been found to be important in developmental processes, as planar polarity is required to define the in-plane tissue coordinate system at the cellular level.

Results

We have built an in-silico functional model of cellular polarisation that includes cellular asymmetry, cell-cell signalling and a response to a global cue. The model has been validated and parameterised against domineering non-autonomous wing hair phenotypes in Drosophila.

Conclusions

We have carried out a systematic comparison of in-silico polarity phenotypes with patterns observed in vivo under different genetic manipulations in the wing. This has allowed us to classify the specific functional roles of proteins involved in generating cell polarity, providing new hypotheses about their specific functions, in particular for Pk and Dsh. The predictions from the model allow direct assignment of functional roles of genes from genetic mosaic analysis of Drosophila wings.

【 授权许可】

   
2013 Hazelwood and Hancock; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Keller R: Shaping the vertebrate body plan by polarised embryonic cell movements. Science 2002, 298:1950-1954.
• [2]Wallingford JB, Fraser SE, Harland RM: Convergent extension: the molecular control of polarised cell movement during embryonic development. Dev Cell 2002, 2:695-706.
• [3]Murdoch JN, Henderson DJ, Doudney K, Gaston-Massuet C, Phillips HM, Paternotte C, Arkell R, Stanier P, Copp AJ: Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Hum Mol Genet 2003, 12:87-98.
• [4]Yates LL, Schnatwinkel C, Murdoch JN, Bogani D, Formstone CJ, Townsend S, Greenfield A, Niswander LA, Dean CH: The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Hum Mol Genet 2010, 19:2251-2267.
• [5]Fischer E, Legue E, Doyen A, Nato F, Nicolas JF, Torres V, Yaniv M, Pontoglio M: Defective planar cell polarity in polycystic kidney disease. Nat Genet 2006, 38:21-23.
• [6]Saburi S, Hester I, Fischer E, Pontoglio M, Eremina V, Gessler M, Quaggin SE, Harrison R, Mount R, McNeill H: Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat Genet 2008, 40:1010-1015.
• [7]Cantrell VA, Jessen JR: The planar cell polarity protein Van Gogh-Like 2 regulates tumor cell migration and matrix metalloproteinase-dependent invasion. Cancer Lett 2010, 287:54-61.
• [8]Vinson CR, Adler PN: Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 1987, 329:549-551.
• [9]Gubb D, García-Bellido A: A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol 1982, 68:37-57.
• [10]Adler PN, Krasnow RE, Liu J: Tissue polarity points from cells that have higher Frizzled levels towards cells that have lower Frizzled levels. Curr Biol 1997, 7:940-949.
• [11]Taylor J, Abramova N, Charlton J, Adler PN: Van Gogh: a new Drosophila tissue polarity gene. Genetics 1998, 150:199-210.
• [12]Usui T, Shima Y, Shimada Y, Hirano S, Burgess RW, Schwarz TL, Takeichi M, Uemura T: Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 1999, 98:585-595.
• [13]Lawrence PA, Casal J, Struhl G: Cell interactions and planar polarity in the abdominal epidermis of Drosophila. Development 2004, 131:4651-4664.
• [14]Strutt D, Strutt H: Differential activities of the core planar polarity proteins during Drosophila wing patterning. Dev Biol 2007, 302:181-194.
• [15]Simons M, Mlodzik M: Planar cell polarity signaling: from fly development to human disease. Annu Rev Genet 2008, 42:517-540.
• [16]Strutt H, Strutt D: Asymmetric localisation of planar polarity proteins: mechanisms and consequences. Semin Cell Dev Biol 2009, 20:957-963.
• [17]Casal J, Lawrence PA, Struhl G: Two separate molecular systems, dachsous/fat and starry night/frizzled, act independently to confer planar cell polarity. Development 2006, 133:4561-4572.
• [18]Lawrence PA, Struhl G, Casal J: Planar cell polarity: one or two pathways? Nat Rev Genet 2007, 8:555-563.
• [19]Strutt D: Gradients and the specification of planar polarity in the insect cuticle. Cold Spring Harb Perspect Biol 2009, 1:a000489.
• [20]Aigouy B, Farhadifar R, Staple DB, Sagner A, Roper JC, Julicher F, Eaton S: Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 2010, 142:773-786.
• [21]Axelrod JD: Progress and challenges in understanding planar cell polarity signaling. Semin Cell Dev Biol 2009, 20:964-971.
• [22]Ma D, Yang CH, McNeill H, Simon MA, Axelrod JD: Fidelity in planar cell polarity signalling. Nature 2003, 421:543-547.
• [23]Tree DR, Ma D, Axelrod JD: A three-tiered mechanism for regulation of planar cell polarity. Semin Cell Dev Biol 2002, 13:217-224.
• [24]Klein TJ, Mlodzik M: Planar cell polarization: an emerging model points in the right direction. Annu Rev Cell Dev Biol 2005, 21:155-176.
• [25]Le Garrec JF, Lopez P, Kerszberg M: Establishment and maintenance of planar epithelial cell polarity by asymmetric cadherin bridges: a computer model. Dev Dyn 2006, 235:235-246.
• [26]Wu J, Mlodzik M: The frizzled extracellular domain is a ligand for Van gogh/stbm during nonautonomous planar cell polarity signaling. Dev Cell 2008, 15:462-469.
• [27]Eaton S, Julicher F: Cell flow and tissue polarity patterns. Curr Opin Genet Dev 2011, 21:1-6.
• [28]Amonlirdviman K, Khare NA, Tree DRP, Chen W-S, Axelrod JD, Tomlin CJ: Mathematical modeling of planar cell polarity to understand domineering non-autonomy. Science 2005, 307:423-426.
• [29]Burak Y, Shraiman BI: Order and stochastic dynamics in Drosophila planar cell polarity. PLoS Comput Biol 2009, 5:e1000628.
• [30]Schamberg S, Houston P, Monk NA, Owen MR: Modelling and analysis of planar cell polarity. Bull Math Biol 2010, 72:645-680.
• [31]Schopohl N, Sluckin TJ: Defect core structure in nematic liquid crystals. Phys Rev Lett 1987, 59:2582-2584.
• [32]Chaikin PM, Lubensky TC: Principles of condensed matter physics. Cambridge: Cambridge University Press; 2000.
• [33]Wang Y, Badea T, Nathans J: Order from disorder: Self-organization in mammalian hair patterning. Proc Natl Acad Sci U S A 2006, 103:19800-19805.
• [34]Zhu H: Is anisotropic propagation of polarized molecular distribution the common mechanism of swirling patterns of planar cell polarization? J Theor Biol 2009, 256:315-325.
• [35]Strutt H, Strutt D: Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled. Dev Cell 2002, 3:851-863.
• [36]Chae J, Kim MJ, Goo JH, Collier S, Gubb D, Charlton J, Adler PN, Park WJ: The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 1999, 126:5421-5429.
• [37]Lee H, Adler PN: The function of the frizzled pathway in the Drosophila wing is dependent on inturned and fuzzy. Genetics 2002, 160:1535-1547.
• [38]Adler P, Charlton J, Liu J: Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling. Development 1998, 125:959-968.
• [39]Adler PN, Taylor J, Charlton J: The domineering non-autonomy of frizzled and Van Gogh clones in the Drosophila wing is a consequence of a disruption in local signalling. Mech Dev 2000, 96:197-207.
• [40]Strutt D, Warrington SJ: Planar polarity genes in the drosophila wing regulate the localisation of the FH3 domain protein multiple wing hairs to control the site of hair production. Development 2008, 135:3103-3111.
• [41]Wong LL, Adler PN: Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol 1993, 123:209-221.
• [42]Krasnow RE, Adler PN: A single frizzled protein has a dual function in tissue polarity. Development 1994, 120:1883-1893.
• [43]Zeidler MP, Perrimon N, Strutt DI: Multiple rôles for four-jointed in planar polarity and limb patterning. Dev Biol 2000, 228:181-196.
• [44]Strutt DI: The asymmetric subcellular localisation of components of the planar polarity pathway. Semin Cell Dev Biol 2002, 13:225-231.
• [45]Zeidler MP, Perrimon N, Strutt DI: The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification. Curr Biol 1999, 9:1363-1372.
• [46]Tomlin CJ, Axelrod JD: Biology by numbers: mathematical modelling in developmental biology. Nat Rev Genet 2007, 8:331-340.
• [47]Turing AM: The chemical basis of morphogenesis. Phil Trans R Soc Lond B Biol Sci 1952, 237:37-72.
• [48]Matakatsu H, Blair SS: Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development 2004, 131:3785-3794.
• [49]Simon MA: Planar cell polarity in the drosophila eye is directed by graded four-jointed and dachsous expression. Development 2004, 131:6175-6184.
• [50]Ma D, Amonlirdviman K, Raffard RL, Abate A, Tomlin CJ, Axelrod JD: Cell packing influences planar cell polarity signaling. Proc Natl Acad Sci U S A 2008, 105:18800-18805.
• [51]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.
• [52]Brittle AL, Repiso A, Casal J, Lawrence PA, Strutt D: Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for fat. Curr Biol 2010, 20:803-810.
• [53]Simon MA, Xu A, Ishikawa HO, Irvine KD: Modulation of fat:dachsous binding by the cadherin domain kinase four-jointed. Curr Biol 2010, 20:811-817.
• [54]Shalaginov AN, Hazelwood LD, Sluckin TJ: Dynamics of chevron structure formation. Phys Rev E 1998, 58:7455-7464.
• [55]Adler PN, Zhu C, Stone D: Inturned localizes to the proximal side of wing cells under the instruction of upstream planar polarity proteins. Curr Biol 2004, 14:2046-2051.
• [56]Yan J, Huen D, Morely T, Johnson G, Gubb D, Roote J, Adler PN: The multiple-wing-hairs gene encodes a novel GBD-FH3 domain-containing protein that functions both prior to and after wing hair initiation. Genetics 2008, 180:219-228.
• [57]Altschuler SJ, Angenent SB, Wang Y, Wu LF: On the spontaneous emergence of cell polarity. Nature 2008, 454:886-889.
• [58]WH Press: Numerical recipes in FORTRAN : the art of scientific computing. 2nd edition. Cambridge: Cambridge University Press; 1992.