Ephrin-Eph signaling in embryonic tissue separation

Cell Adhesion and Migration

Volumn 8, Issue 4, 2014, Pages 308-326

  Fagotto, Francois ^a   Winklbauer, Rudolf ^b   Rohani, Nazanin ^a  

^a MCGILL UNIVERSITY   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Cell adhesion; Cell sorting; Contact inhibition; Differential adhesion; Embryonic development; Morphogenesis; Signaling

Indexed keywords

EPHRIN; EPHRIN RECEPTOR;

AMBIGUITY; CELL ADHESION; CELL POPULATION; CELL SURFACE; ECTODERM; EMBRYO CELL; EMBRYO DEVELOPMENT; EMBRYONAL TISSUE; ENZYME ACTIVITY; ENZYME MECHANISM; EYE MALFORMATION; GASTRULA; INVERTEBRATE; MESODERM; NONHUMAN; NOTOCHORD; PHENOTYPIC VARIATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; RHOMBENCEPHALON; SIGNAL TRANSDUCTION; SOMITE; TISSUE DIFFERENTIATION; ANIMAL; BIOLOGICAL MODEL; CELL MOTION; CHICK EMBRYO; METABOLISM; MORPHOGENESIS; MOUSE; XENOPUS; ZEBRA FISH;

ANIMALS; CELL ADHESION; CELL MOVEMENT; CHICK EMBRYO; EMBRYONIC DEVELOPMENT; EPHRINS; MICE; MODELS, BIOLOGICAL; MORPHOGENESIS; RECEPTORS, EPH FAMILY; SIGNAL TRANSDUCTION; XENOPUS; ZEBRAFISH;

EID: 84919905025     PISSN: 19336918     EISSN: 19336926     Source Type: Journal    
DOI: 10.4161/19336918.2014.970028     Document Type: Review

References (128)

1. Tepass U, Godt D, Winklbauer R. Cell sorting in animal development: signalling and adhesive mechanisms in the formation of tissue boundaries. Curr Opin Genet Dev 2002;12:572-82; PMID:12200163; http://dx.doi.org/10.1016/S0959-437X (02) 00342-8
2. Dahmann C, Oates AC, Brand M. Boundary formation and maintenance in tissue development. Nat Rev Genet 2011;12:43-55; PMID:21164524; http://dx. doi.org/10.1038/nrg2902
3. Krens SF, Heisenberg CP. Cell sorting in development. Curr Top Dev Biol 2011;95:189-213; PMID:21501752; http://dx.doi.org/10.1016/B978-0-12-385065-2.00006-2
4. Batlle E, Wilkinson DG. Molecular mechanisms of cell segregation and boundary formation in development and tumorigenesis. Cold Spring Harb Perspect Biol 2012;4:a008227; PMID:22214769; http://dx. doi.org/10.1101/cshperspect.a008227
5. Bottger A, Hassel M. Hydra, a model system to trace the emergence of boundaries in developing eumetazoans. Int J Dev Biol 2012;56:583-91; PMID:22689360; http://dx.doi.org/10.1387/ijdb.113454ab
6. Holtfreter J. Gewebsaffinität, ein Mittel der embryonalen Formbildung. Arch Exp Zellforsch Gewebeszücht 1939;23:169-209.
7. Holtfreter J. A study of the mechanics of gastrulation. J Exp Zool 1944;95:171-212; http://dx.doi.org/10.1002/jez.1400950203
8. Townes PL, Holtfreter J. Directed movements and selective adhesion of embryonic amphibian cells. J Exp Zool 1955;128:53-120; http://dx.doi.org/10.1002/jez.1401280105
9. Steinberg MS. Reconstruction of tissues by dissociated cells. Some morphogenetic tissue movements and the sorting out of embryonic cells may have a common explanation. Science 1963;141:401-8; PMID:13983728; http://dx.doi.org/10.1126/science.141.3579.401
10. Steinberg MS. Does differential adhesion govern self-assembly processes in histogenesis? Equilibrium configurations and the emergence of a hierarchy among populations of embryonic cells. J Exp Zool 1970;173:395-434; PMID:5429514; http://dx.doi.org/10.1002/jez.1401730406
11. Foty RA, Steinberg MS. The differential adhesion hypothesis: a direct evaluation. Dev Biol 2005;278:255-63; PMID:15649477; http://dx.doi.org/10.1016/j.ydbio.2004.11.012
12. Edelman GM. Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu Rev Cell Biol 1986;2:81-116; PMID:3548776; http://dx.doi.org/10.1146/annurev. cb.02.110186.000501
13. Takeichi M. Morphogenetic roles of classic cadherins. [Review]. Curr Op Cell Biol 1995;7:619-27; PMID:8573335; http://dx.doi.org/10.1016/0955-0674 (95) 80102-2
14. Foty RA, Steinberg MS. Cadherin-mediated cell-cell adhesion and tissue segregation in relation to malignancy. Int J Dev Biol 2004;48:397-409; PMID: 15349815; http://dx.doi.org/10.1387/ijdb.041810rf
15. Niessen CM, Gumbiner BM. Cadherin-mediated cell sorting not determined by binding or adhesion specificity. J Cell Biol 2002;156:389-99; http://dx.doi.org/10.1083/jcb.200108040
16. Shi Q, Chien YH, Leckband D. Biophysical properties of cadherin bonds do not predict cell sorting. J Biol Chem 2008;283:28454-63; PMID:18552401; http://dx.doi.org/10.1074/jbc. M802563200
17. Youssef J, Nurse AK, Freund LB, Morgan JR. Quantification of the forces driving self-assembly of three-dimensional microtissues. Proc Natl Acad Sci U S A 2011;108:6993-8; PMID:21482784; http://dx.doi.org/10.1073/pnas.1102559108
18. Maitre JL, Berthoumieux H, Krens SF, Salbreux G, Julicher F, Paluch E, Heisenberg CP. Adhesion Functions in Cell Sorting by Mechanically Coupling the Cortices of Adhering Cells. Science 2012;338:253-6; PMID:22923438; http://dx.doi.org/10.1126/science. 1225399
19. Harris AK. Is Cell sorting caused by differences in the work of intercellular adhesion? A critique of the Steinberg hypothesis. J Theor Biol 1976;61:267-85; PMID:985668; http://dx.doi.org/10.1016/0022-5193 (76) 90019-9
20. Brodland GW. The Differential Interfacial Tension Hypothesis (DITH): a comprehensive theory for the self-rearrangement of embryonic cells and tissues. J Biomech Eng 2002;124:188-97; PMID:12002128; http://dx.doi.org/10.1115/1.1449491
21. Brodland GW, Yang J, Sweny J. Cellular interfacial and surface tensions determined from aggregate compression tests using a finite element model. HFSP J 2009;3:273-81; PMID:20057960; http://dx.doi.org/10.2976/1.3175812
22. Manning BD, Barrett JG, Wallace JA, Granok H, Snyder M. Differential regulation of the Kar3p kinesin-related protein by two associated proteins, Cik1p and Vik1p. J Cell Biol 1999;144:1219-33; PMID: 10087265; http://dx.doi.org/10.1083/jcb.144.6.1219
23. Krieg M, Arboleda-Estudillo Y, Puech PH, Kafer J, Graner F, Muller DJ, Heisenberg CP. Tensile forces govern germ-layer organization in zebrafish. Nat Cell Biol 2008;10:429-36; PMID:18364700; http://dx. doi.org/10.1038/ncb1705
24. Steinberg MS, Takeichi M. Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression. Proc Natl Acad Sci USA 1994;91:206-9; PMID:8278366; http://dx.doi.org/10.1073/pnas.91.1.206
25. Ninomiya H, David R, Damm EW, Fagotto F, Niessen CM, Winklbauer R. Cadherin-dependent differential cell adhesion in Xenopus causes cell sorting in vitro but not in the embryo. J Cell Sci 2012;125:1877-83; PMID:22328523; http://dx.doi.org/10.1242/jcs.095315
26. Landsberg KP, Farhadifar R, Ranft J, Umetsu D, Widmann TJ, Bittig T, Said A, Julicher F, Dahmann C. Increased cell bond tension governs cell sorting at the Drosophila anteroposterior compartment boundary. Curr Biol 2009;19:1950-5; PMID:19879142; http://dx.doi.org/10.1016/j.cub.2009.10.021
27. Winklbauer R. Cell adhesion in amphibian gastrulation. Int Rev Cell Mol Biol 2009;278:215-75; PMID:19815180; http://dx.doi.org/10.1016/S1937-6448 (09) 78005-0
28. Xu Q, Wilkinson DG. Boundary formation in the development of the vertebrate hindbrain. Wiley Interdisc Rev Dev Biol 2013;2:735-45; http://dx.doi.org/10.1002/wdev. 106
29. Flanagan JG, Vanderhaeghen P. The ephrins and Eph receptors in neural development. Annu Rev Neurosci 1998;21:309-45; PMID:9530499; http://dx.doi.org/10.1146/annurev. neuro.21.1.309
30. Klein R. Eph/ephrin signaling in morphogenesis, neural development and plasticity. Curr Op Cell Biol 2004;16:580-9; PMID:15363810; http://dx.doi.org/10.1016/j.ceb.2004.07.002
31. Pasquale EB. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 2010;10:165-80; PMID:20179713; http://dx.doi.org/10.1038/nrc2806
32. Durbin L, Brennan C, Shiomi K, Cooke J, Barrios A, Shanmugalingam S, Guthrie B, Lindberg R, Holder N. Eph signaling is required for segmentation and differentiation of the somites. Genes Dev 1998;12:3096-109; PMID:9765210; http://dx.doi.org/10.1101/gad.12.19.3096
33. Xu Q, Mellitzer G, Robinson V, Wilkinson DG. In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 1999;399:267-71; PMID:10353250; http://dx.doi.org/10.1038/20452
34. Mellitzer G, Xu Q, Wilkinson D. Eph receptors and ephrins restrict cell intermingling and communication. Nature 1999;400:77-81; PMID:10403252; http://dx.doi.org/10.1038/21907
35. Rohani N, Canty L, Luu O, Fagotto F, Winklbauer R. EphrinB/EphB signaling controls embryonic germ layer separation by contact-induced cell detachment. PLoS Biol 2011;9:e1000597; PMID:21390298; http://dx.doi.org/10.1371/journal.pbio.1000597
36. Fagotto F, Rohani N, Touret AS, Li R. A molecular base for cell sorting at embryonic boundaries: contact inhibition of cadherin adhesion by ephrin/Ephdependent contractility. Dev Cell 2013;27:72-87; PMID:24094740; http://dx.doi.org/10.1016/j. devcel.2013.09.004
37. Cavodeassi F, Ivanovitch K, Wilson SW. Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis. Development 2013;140:4193-202; PMID:24026122; http://dx.doi.org/10.1242/dev. 097048
38. Park EC, Cho GS, Kim GH, Choi SC, Han JK. The involvement of Eph-Ephrin signaling in tissue separation and convergence during Xenopus gastrulation movements. Dev Biol 2011;350:441-50; PMID:21147090; http://dx.doi.org/10.1016/j.ydbio.2010.12.012
39. Cooke JE, Kemp HA, Moens CB. EphA4 is required for cell adhesion and rhombomere boundary formation in the zebrafish. Curr Biol 2005;15:536-42; PMID:15797022; http://dx.doi.org/10.1016/j. cub.2005.02.019
40. Kemp HA, Cooke JE, Moens CB. EphA4 and EfnB2a maintain rhombomere coherence by independently regulating intercalation of progenitor cells in the zebrafish neural keel. Dev Biol 2009;327:313-26; PMID:19135438; http://dx.doi.org/10.1016/j. ydbio.2008.12.010
41. Barrios A, Poole RJ, Durbin L, Brennan C, Holder N, Wilson SW. Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Curr Biol 2003;13:1571-82; PMID:13678588; http://dx.doi.org/10.1016/j.cub.2003.08.030
42. Watanabe T, Sato Y, Saito D, Tadokoro R, Takahashi Y. EphrinB2 coordinates the formation of a morphological boundary and cell epithelialization during somite segmentation. Proc Natl Acad Sci USA 2009;106:7467-72; PMID:19380726; http://dx.doi.org/10.1073/pnas.0902859106
43. Jungbluth S, Larsen C, Wizenmann A, Lumsden A. Cell mixing between the embryonic midbrain and hindbrain. Curr Biol 2001;11:204-7; PMID:11231158; http://dx.doi.org/10.1016/S0960-9822 (01) 00049-5
44. Reintsch WE, Habring-Mueller A, Wang RW, Schohl A, Fagotto F. β-Catenin controls cell sorting at the notochord-somite boundary independently of cadherin-mediated adhesion. J Cell Biol 2005;170:675-86; PMID:16103232; http://dx.doi.org/10.1083/jcb.200503009
45. Takahashi Y, Sato Y. Somitogenesis as a model to study the formation of morphological boundaries and cell epithelialization. Dev Growth Differ 2008;50 Suppl 1:S149-55; PMID:18482400; http://dx.doi.org/10.1111/j.1440-169X.2008.01018.x
46. Maroto M, Bone RA, Dale JK. Somitogenesis. Development 2012;139:2453-6; PMID:22736241; http://dx.doi.org/10.1242/dev. 069310
47. Rohani N, Parmeggiani A, Winklbauer R, Fagotto F. Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation. PloS Biol 2014;12:e1001955; http://dx.doi.org/10.1371/journal.pbio.1001955
48. Baker RK, Antin PB. Ephs and ephrins during early stages of chick embryogenesis. Dev Dyn 2003;228:128-42; PMID:12950087; http://dx.doi.org/10.1002/dvdy.10354
49. Aulehla A, Pourquie O. Oscillating signaling pathways during embryonic development. Curr Opin Cell Biol 2008;20:632-7; PMID:18845254; http://dx.doi.org/10.1016/j.ceb.2008.09.002
50. Davy A, Soriano P. Ephrin-B2 forward signaling regulates somite patterning and neural crest cell development. Dev Biol 2007;304:182-93; PMID:17223098; http://dx.doi.org/10.1016/j.ydbio.2006.12.028
51. Helbling PM, Saulnier DM, Brandli AW. The receptor tyrosine kinase EphB4 and ephrin-B ligands restrict angiogenic growth of embryonic veins in Xenopus laevis. Development 2000;127:269-78; PMID:10603345
52. Chan J, Mably JD, Serluca FC, Chen JN, Goldstein NB, Thomas MC, Cleary JA, Brennan C, Fishman MC, Roberts TM. Morphogenesis of prechordal plate and notochord requires intact Eph/ephrin B signaling. Dev Biol 2001;234:470-82; http://dx.doi.org/10.1006/dbio.2001.0281
53. Chen J, Ruley HE. An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins. J Biol Chem 1998;273:24670-5; PMID:9733765; http://dx.doi.org/10.1074/jbc.273.38.24670
54. Prin F, Serpente P, Itasaki N, Gould AP. Hox proteins drive cell segregation and non-autonomous apical remodelling during hindbrain segmentation. Development 2014;141:1492-502; PMID:24574009; http://dx.doi.org/10.1242/dev. 098954
55. Xu Q, Alldus G, Holder N, Wilkinson DG. Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain. Development 1995;121:4005-16; PMID:8575301
56. Cooke J, Moens C, Roth L, Durbin L, Shiomi K, Brennan C, Kimmel C, Wilson S, Holder N. Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain. Development 2001;128:571-80; PMID:11171340
57. Heasman J. Morpholino oligos: making sense of antisense? Dev Biol 2002;243:209-14; PMID:11884031; http://dx.doi.org/10.1006/dbio.2001.0565
58. Calzolari S, Terriente J, Pujades C. Cell segregation in the vertebrate hindbrain relies on actomyosin cables located at the interhombomeric boundaries. EMBO J 2014;33:686-701; PMID:24569501; http://dx.doi.org/10.1002/embj.201386003
59. Durbin L, Sordino P, Barrios A, Gering M, Thisse C, Thisse B, Brennan C, Green A, Wilson S, Holder N. Anteroposterior patterning is required within segments for somite boundary formation in developing zebrafish. Development 2000;127:1703-13; PMID:10725246
60. Wacker S, Grimm K, Joos T, Winklbauer R. Development and Control of Tissue Separation at Gastrulation in Xenopus. Dev Biol 2000;224:428-39; PMID:10926778; http://dx.doi.org/10.1006/dbio.2000.9794
61. Winklbauer R, Luu O. Frizzled-7-dependent tissue separation in the Xenopus gastrula. Methods Mol Biol 2008;469:485-92; PMID:19109728; http://dx. doi.org/10.1007/978-1-60327-469-2-31
62. Blits-Huizinga CT, Nelersa CM, Malhotra A, Liebl DJ. Ephrins and their receptors: binding versus biology. IUBMB Life 2004;56:257-65; PMID:15370889; http://dx.doi.org/10.1080/15216540412331270076
63. Day B, To C, Himanen JP, Smith FM, Nikolov DB, Boyd AW, Lackmann M. Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3. J Biol Chem 2005;280:26526-32; PMID:15901737; http://dx.doi.org/10.1074/jbc. M504972200
64. Pabbisetty KB, Yue X, Li C, Himanen JP, Zhou R, Nikolov DB, Hu L. Kinetic analysis of the binding of monomeric and dimeric ephrins to Eph receptors: correlation to function in a growth cone collapse assay. CA>Protein Sci 2007;16:355-61; http://dx. doi.org/10.1110/ps.062608807
65. Noberini R, Rubio De La Torre E, Pasquale EB. Profiling Eph receptor expression in cells and tissues: a targeted mass spectrometry approach. Cell Adh Migr 2012;6:102-12; PMID:22568954; http://dx.doi.org/10.4161/cam.19620
66. Flanagan JG, Vanderhaeghen P. The ephrins and Eph receptors in neural development. Annu Rev Neurosci 2003;21:309-45; http://dx.doi.org/10.1146/annurev. neuro.21.1.309
67. Surawska H, Ma PC, Salgia R. The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev 2004;15:419-33; PMID:15561600; http://dx. doi.org/10.1016/j.cytogfr.2004.09.002
68. Astin JW, Batson J, Kadir S, Charlet J, Persad RA, Gillatt D, Oxley JD, Nobes CD. Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells. Nat Cell Biol 2010;12:1194-204; PMID:21076414; http://dx.doi.org/10.1038/ncb2122
69. Schaupp A, Sabet O, Dudanova I, Ponserre M, Bastiaens P, Klein R. The composition of EphB2 clusters determines the strength in the cellular repulsion response. J Cell Biol 2014;204:409-22; PMID:24469634; http://dx.doi.org/10.1083/jcb.201305037
70. Zimmer M, Palmer A, Kohler J, Klein R. EphB-ephrinB bi-directional endocytosis terminates adhesion allowing contact mediated repulsion. Nat Cell Biol 2003;5:869-78; PMID:12973358; http://dx.doi.org/10.1038/ncb1045
71. Marston DJ, Dickinson S, Nobes CD. Rac-dependent trans-endocytosis of ephrinBs regulates Eph-ephrin contact repulsion. Nat Cell Biol 2003;5:879-88; PMID:12973357; http://dx.doi.org/10.1038/ncb 1044
72. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005;123:291-304; PMID:16239146; http://dx.doi.org/10.1016/j.cell.2005.08.014
73. Wimmer-Kleikamp SH, Nievergall E, Gegenbauer K, Adikari S, Mansour M, Yeadon T, Boyd AW, Patani NR, Lackmann M. Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells. Blood 2008;112:721-32; PMID:18385452; http://dx.doi.org/10.1182/blood-2007-11-121681
74. Halloran MC, Wolman MA. Repulsion or adhesion: receptors make the call. Curr Opin Cell Biol 2006;18:533-40; PMID:16930978; http://dx.doi.org/10.1016/j.ceb.2006.08.010
75. Arvanitis D, Davy A. Eph/ephrin signaling: networks. Genes Dev 2008;22:416-29; PMID:18281458; http://dx.doi.org/10.1101/gad.1630408
76. Dravis C, Yokoyama N, Chumley MJ, Cowan CA, Silvany RE, Shay J, Baker LA, Henkemeyer M. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol 2004;271:272-90; PMID:15223334; http://dx.doi.org/10.1016/j.ydbio.2004.03.027
77. Senturk A, Pfennig S, Weiss A, Burk K, Acker-Palmer A. Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration. Nature 2011;472:356-60; PMID:21460838; http://dx.doi.org/10.1038/nature09874
78. Dottori M, Hartley L, Galea M, Paxinos G, Polizzotto M, Kilpatrick T, Bartlett PF, Murphy M, Kontgen F, Boyd AW. EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract. Proc Natl Acad Sci U S A 1998;95:13248-53; PMID:9789074; http://dx.doi.org/10.1073/pnas.95.22.13248
79. Medina A, Swain RK, Kuerner KM, Steinbeisser H. Xenopus paraxial protocadherin has signaling functions and is involved in tissue separation. EMBO J 2004;23:3249-58; PMID:15272309; http://dx.doi.org/10.1038/sj.emboj.7600329
80. Kim SH, Yamamoto A, Bouwmeester T, Agius E, Robertis EM. The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation. Development 1998;125:4681-90; PMID:9806917
81. Yamamoto A, Amacher SL, Kim SH, Geissert D, Kimmel CB, De Robertis EM. Zebrafish paraxial protocadherin is a downstream target of spadetail involved in morphogenesis of gastrula mesoderm. Development 1998;125:3389-97; PMID:9693142
82. Yamamoto A, Kemp C, Bachiller D, Geissert D, De Robertis EM. Mouse paraxial protocadherin is expressed in trunk mesoderm and is not essential for mouse development. Genesis 2000;27:49-57.
83. Kim SH, Jen WC, De Robertis EM, Kintner C. The protocadherin PAPC establishes segmental boundaries during somitogenesis in Xenopus embryos. Curr Biol 2000.
84. Sawada A, Fritz A, Jiang YJ, Yamamoto A, Yamasu K, Kuroiwa A, Saga Y, Takeda H. Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites. Development 2000;127:1691-702; PMID:10725245
85. Rhee J, Takahashi Y, Saga Y, Wilson-Rawls J, Rawls A. The protocadherin papc is involved in the organization of the epithelium along the segmental border during mouse somitogenesis. Dev Biol 2003;254:248-61; PMID:12591245; http://dx.doi.org/10.1016/S0012-1606 (02) 00085-4
86. Chung HA, Yamamoto TS, Ueno N. ANR5, an FGF Target Gene Product, Regulates Gastrulation in Xenopus. Curr Biol 2007;17:932-9; PMID:17475493; http://dx.doi.org/10.1016/j.cub.2007.04.034
87. Winklbauer R, Medina A, Swain RK, Steinbeisser H. Frizzled-7 signalling controls tissue separation during Xenopus gastrulation. Nature 2001;413:856-60; PMID:11677610; http://dx.doi.org/10.1038/35101621
88. Hukriede NA, Tsang TE, Habas R, Khoo PL, Steiner K, Weeks DL, Tam PP, Dawid IB. Conserved requirement of Lim1 function for cell movements during gastrulation. Dev Cell 2003;4:83-94; PMID:12530965; http://dx.doi.org/10.1016/S1534-5807 (02) 00398-2
89. Maghzal N, Vogt E, Reintsch W, Fraser JS, Fagotto F. The tumor associated EpCAM regulates morphogenetic movements through intracellular signaling. J Cell Biol 2010;119:645-59; http://dx.doi.org/10.1083/jcb.201004074
90. Chen X, Gumbiner BM. Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity. J Cell Biol 2006;174:301-13; PMID:16847104; http://dx.doi.org/10.1083/jcb.200602062
91. Chen X, Koh E, Yoder M, Gumbiner BM. A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis. PLoS ONE 2009;4:e8411; PMID:20027292; http://dx.doi.org/10.1371/journal. pone.0008411
92. Kraft B, Berger CD, Wallkamm V, Steinbeisser H, Wedlich D. Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin. J Cell Biol 2012;198:695-709; PMID:22908314; http://dx.doi.org/10.1083/jcb.201110076
93. Unterseher F, Hefele JA, Giehl K, De Robertis EM, Wedlich D, Schambony A. Paraxial protocadherin coordinates cell polarity during convergent extension via Rho A and JNK. EMBO J 2004;23:3259-69; PMID:15297873; http://dx.doi.org/10.1038/sj. emboj.7600332
94. Wang Y, Janicki P, Koster I, Berger CD, Wenzl C, Grosshans J, Steinbeisser H. Xenopus Paraxial Protocadherin regulates morphogenesis by antagonizing Sprouty. Genes Dev 2008;22:878-83; PMID: 18381892; http://dx.doi.org/10.1101/gad.452908
95. Kietzmann A, Wang Y, Weber D, Steinbeisser H. Xenopus paraxial protocadherin inhibits Wnt/β-catenin signalling via casein kinase 2beta. EMBO Rep. 2012;13:129-34; PMID:22193776; http://dx.doi.org/10.1038/embor.2011.240
96. Kao TJ, Kania A. Ephrin-mediated cis-attenuation of Eph receptor signaling is essential for spinal motor axon guidance. Neuron 2011;71:76-91; PMID: 21745639; http://dx.doi.org/10.1016/j.neuron. 011.05.031
97. Xu Q, Wilkinson DG. Eph-related receptors and their ligands: mediators of contact dependent cell interactions. J Mol Med 1997;75:576-86; PMID:9297625; http://dx.doi.org/10.1007/s001090050142
98. Glazier JA, Zhang Y, Swat M, Zaitlen B, Schnell S. Coordinated action of N-CAM, N-cadherin, EphA4, and ephrinB2 translates genetic prepatterns into structure during somitogenesis in chick. Curr Top Dev Biol 2008;81:205-47; PMID:18023729; http://dx. doi.org/10.1016/S0070-2153 (07) 81007-6
99. Fagotto F. The cellular basis of tissue separation. Development; 2014;141:3303-3318. http://dx.doi.org/10.1242/dev. 090332
100. Luu O, David R, Ninomiya H, Winklbauer R. Largescale mechanical properties of Xenopus embryonic epithelium. Proc Natl Acad Sci U S A 2011;108:4000-5; PMID:21368110; http://dx.doi.org/10.1073/pnas.1010331108
101. Aliee M, Roper JC, Landsberg KP, Pentzold C, Widmann TJ, Julicher F, Dahmann C. Physical mechanisms shaping the Drosophila dorsoventral compartment boundary. Curr Biol 2012;22:967-76; PMID:22560616; http://dx. doi.org/10.1016/j.cub.2012.03.070
102. Julich D, Mould AP, Koper E, Holley SA. Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling. Development 2009;136:2913-21; PMID:19641014; http://dx.doi.org/10.1242/dev. 038935
103. Richter DJ, King N. The genomic and cellular foundations of animal origins. Annu Rev Genet 2013;47:509-37; PMID:24050174; http://dx.doi.org/10.1146/annurev-genet-111212-133456
104. Mellott DO, Burke RD. The molecular phylogeny of eph receptors and ephrin ligands. BMC Cell Biol 2008;9:27; PMID:18495034; http://dx.doi.org/10.1186/1471-2121-9-27
105. Reddy PC, Bidaye SS, Ghaskadbi S. Genome-wide screening reveals the emergence and divergence of RTK homologues in basal Metazoan Hydra magnipapillata. J Biosci 2011;36:289-96; PMID:21654083; http://dx.doi.org/10.1007/s12038-011-9065-6
106. Chang LH, Chen P, Lien MT, Ho YH, Lin CM, Pan YT, Wei SY, Hsu JC. Differential adhesion and actomyosin cable collaborate to drive Echinoid-mediated cell sorting. Development 2011;138:3803-12; PMID:21795280; http://dx.doi.org/10.1242/dev. 062257
107. Laplante C, Nilson LA. Asymmetric distribution of Echinoid defines the epidermal leading edge during Drosophila dorsal closure. J Cell Biol 2011;192:335-48; PMID:21263031; http://dx.doi.org/10.1083/jcb.201009022
108. Lin HP, Chen HM, Wei SY, Chen LY, Chang LH, Sun YJ, Huang SY, Hsu JC. Cell adhesion molecule Echinoid associates with unconventional myosin VI/Jaguar motor to regulate cell morphology during dorsal closure in Drosophila. Dev Biol 2007;311:423-33; PMID:17936269; http://dx.doi.org/10.1016/j. ydbio.2007.08.043
109. Theil T, Frain M, Gilardi-Hebenstreit P, Flenniken A, Charnay P, Wilkinson DG. Segmental expression of the EphA4 (Sek-1) receptor tyrosine kinase in the hindbrain is under direct transcriptional control of Krox-20. Development 1998;125:443-52; PMID: 9425139
110. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet 1993;9:317-21; PMID:8236461; http://dx.doi.org/10.1016/0168-9525 (93) 90250-L
111. Himanen JP, Rajashankar KR, Lackmann M, Cowan CA, Henkemeyer M, Nikolov DB. Crystal structure of an Eph receptor-ephrin complex. Nature 2001;414:933-8; PMID:11780069; http://dx.doi.org/10.1038/414933a
112. Nikolov DB, Li C, Barton WA, Himanen JP. Crystal structure of the ephrin-B1 ectodomain: implications for receptor recognition and signaling. Biochemistry 2005;44:10947-53; PMID:16101278; http://dx.doi.org/10.1021/bi050789w
113. Stein E, Huynh-Do U, Lane AA, Cerretti DP, Daniel TO. Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun. kinase. J Biol Chem 1998;273:1303-8; PMID:9430661; http://dx.doi.org/10.1074/jbc.273.3.1303
114. Himanen JP, Nikolov DB. Eph signaling: a structural view. Trends Neurosci 2003;26:46-51; PMID:12495863; http://dx.doi.org/10.1016/S0166-2236 (02) 00005-X
115. Coulthard MG, Lickliter JD, Subanesan N, Chen K, Webb GC, Lowry AJ, Koblar S, Bottema CD, Boyd AW. Characterization of the Epha1 receptor tyrosine kinase: expression in epithelial tissues. Growth Fact 2001;18:303-17; PMID:11519828; http://dx.doi.org/10.3109/08977190109029118
116. Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE, Henkemeyer M, Strebhardt K, Hirai H, Wilkinson DG, et al. Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 1996;17:9-19; PMID:8755474; http://dx.doi.org/10.1016/S0896-6273 (00) 80276-7
117. Janis LS, Cassidy RM, Kromer LF. Ephrin-A binding and EphA receptor expression delineate the matrix compartment of the striatum. J Neurosci 1999;19:4962-71; PMID:10366629
118. Smith FM, Vearing C, Lackmann M, Treutlein H, Himanen J, Chen K, Saul A, Nikolov D, Boyd AW. Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen. J Biol Chem 2004;279:9522-31; PMID:14660665; http://dx.doi.org/10.1074/jbc. M309326200
119. Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, Matsuo K. Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J Biol Chem 2009;284:14637-44; PMID:19299512; http://dx.doi.org/10.1074/jbc. M807598200
120. Nakamoto M. Eph receptors and ephrins. Int J Biochem Cell Biol 2000;32:7-12; PMID:10661890; http://dx.doi.org/10.1016/S1357-2725 (99) 00096-5
121. Himanen JP, Goldgur Y, Miao H, Myshkin E, Guo H, Buck M, Nguyen M, Rajashankar KR, Wang B, Nikolov DB. Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex. EMBO Rep 2009;10:722-8; PMID:19525919; http://dx.doi.org/10.1038/embor.2009.91
122. Nieto MA, Gilardi-Hebenstreit P, Charnay P, Wilkinson DG. A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm. Development 1992;116:1137-50; PMID:1295734
123. Becker N, Seitanidou T, Murphy P, Mattei MG, Topilko P, Nieto MA, Wilkinson DG, Charnay P, Gilardi-Hebenstreit P. Several receptor tyrosine kinase genes of the Eph family are segmentally expressed in the developing hindbrain. Mech Dev 1994;47:3-17; PMID:7947319; http://dx.doi.org/10.1016/0925-4773 (94) 90091-4
124. Bergemann AD, Cheng HJ, Brambilla R, Klein R, Flanagan JG. ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites. Mol Cell Biol 1995;15:4921-9; PMID:7651410
125. Helbling PM, Saulnier DM, Robinson V, Christiansen JH, Wilkinson DG, Brandli AW. Comparative analysis of embryonic gene expression defines potential interaction sites for Xenopus EphB4 receptors with ephrin-B ligands. Dev Dyn 1999;216:361-73; PMID:10633856; http://dx.doi.org/10.1002/(SICI) 1097-0177 (199912) 216:4/5%3c361::AID-DVDY5%3e3.0. CO;2-W
126. Smith A, Robinson V, Patel K, Wilkinson DG. The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. Curr Biol 1997;7:561-70; PMID:9259557; http://dx.doi.org/10.1016/S0960-9822 (06) 00255-7
127. Manzanares M, Trainor PA, Nonchev S, Ariza-McNaughton L, Brodie J, Gould A, Marshall H, Morrison A, Kwan CT, Sham MH, et al. The role of kreisler in segmentation during hindbrain development. Dev Biol 1999;211:220-37; PMID:10395784; http://dx.doi.org/10.1006/dbio.1999.9318
128. Helbling PM, Tran CT, Brandli AW. Requirement for EphA receptor signaling in the segregation of Xenopus third and fourth arch neural crest cells. Mech Dev 1998;78:63-79; PMID:9858686; http://dx.doi.org/10.1016/S0925-4773 (98) 00148-8