Tissue-specific transcription regulators emerged as key developmental control genes, which operate in the context of complex gene regulatory networks (GRNs) to coordinate progressive cell fate specification and tissue morphogenesis. We discuss how GRNs control the individual cell behaviors underlying complex morphogenetic events. Cell behaviors classically range from mesenchymal cell motility to cell shape changes in epithelial sheets. These behaviors emerge from the tissue-specific, multiscale integration of the local activities of universal and pleiotropic effectors, which underlie modular subcellular processes including cytoskeletal dynamics, cell-cell and cell-matrix adhesion, signaling, polarity, and vesicle trafficking. Extrinsic cues and intrinsic cell competence determine the subcellular spatiotemporal patterns of effector activities. GRNs influence most subcellular activities by controlling only a fraction of the effector-coding genes, which we argue is enriched in effectors involved in reading and processing the extrinsic cues to contextualize intrinsic subcellular processes and canalize developmental cell behaviors. The properties of the transcription-cell behavior interface have profound implications for evolution and disease.


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Literature Cited

  1. Abbruzzese G, Becker SF, Kashef J, Alfandari D. 2016. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. Dev. Biol. 415:383–90 [Google Scholar]
  2. Abitua PB, Wagner E, Navarrete IA, Levine M. 2012. Identification of a rudimentary neural crest in a non-vertebrate chordate. Nature 492:104–7 [Google Scholar]
  3. Aman A, Piotrowski T. 2008. Wnt/beta-catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression. Dev. Cell 15:749–61 [Google Scholar]
  4. Anderson DC, Gill JS, Cinalli RM, Nance J. 2008. Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-6 from cell contacts. Science 320:1771–74 [Google Scholar]
  5. Assaker G, Ramel D, Wculek SK, Gonzalez-Gaitan M, Emery G. 2010. Spatial restriction of receptor tyrosine kinase activity through a polarized endocytic cycle controls border cell migration. PNAS 107:22558–63 [Google Scholar]
  6. Bakal C, Aach J, Church G, Perrimon N. 2007. Quantitative morphological signatures define local signaling networks regulating cell morphology. Science 316:1753–56 [Google Scholar]
  7. Bakal C, Perrimon N. 2010. Realizing the promise of RNAi high throughput screening. Dev. Cell 18:506–7 [Google Scholar]
  8. Barsi JC, Tu Q, Davidson EH. 2014. General approach for in vivo recovery of cell type–specific effector gene sets. Genome Res 24:860–68 [Google Scholar]
  9. Bastock R, Strutt D. 2007. The planar polarity pathway promotes coordinated cell migration during Drosophila oogenesis. Development 134:3055–64 [Google Scholar]
  10. Bertet C, Sulak L, Lecuit T. 2004. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429:667–71 [Google Scholar]
  11. Bhuin T, Roy JK. 2014. Rab proteins: the key regulators of intracellular vesicle transport. Exp. Cell Res. 328:1–19 [Google Scholar]
  12. Bianco A, Poukkula M, Cliffe A, Mathieu J, Luque CM. et al. 2007. Two distinct modes of guidance signalling during collective migration of border cells. Nature 448:362–65 [Google Scholar]
  13. Blanchoin L, Boujemaa-Paterski R, Sykes C, Plastino J. 2014. Actin dynamics, architecture, and mechanics in cell motility. Physiol. Rev. 94:235–63 [Google Scholar]
  14. Blankenship JT, Backovic ST, Sanny JS, Weitz O, Zallen JA. 2006. Multicellular rosette formation links planar cell polarity to tissue morphogenesis. Dev. Cell 11:459–70 [Google Scholar]
  15. Bonneau R. 2008. Learning biological networks: from modules to dynamics. Nat. Chem. Biol. 4:658–64 [Google Scholar]
  16. Borghese L, Fletcher G, Mathieu J, Atzberger A, Eades WC. et al. 2006. Systematic analysis of the transcriptional switch inducing migration of border cells. Dev. Cell 10:497–508 [Google Scholar]
  17. Cai D, Chen SC, Prasad M, He L, Wang X. et al. 2014. Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration. Cell 157:1146–59 [Google Scholar]
  18. Cavey M, Rauzi M, Lenne PF, Lecuit T. 2008. A two-tiered mechanism for stabilization and immobilization of E-cadherin. Nature 453:751–56 [Google Scholar]
  19. Chan E, Nance J. 2013. Mechanisms of CDC-42 activation during contact-induced cell polarization. J. Cell Sci. 126:1692–702 [Google Scholar]
  20. Christiaen L, Davidson B, Kawashima T, Powell W, Nolla H. et al. 2008. The transcription/migration interface in heart precursors of Ciona intestinalis. Science 320:1349–52 [Google Scholar]
  21. Christiaen L, Stolfi A, Levine M. 2010. BMP signaling coordinates gene expression and cell migration during precardiac mesoderm development. Dev. Biol. 340:179–87 [Google Scholar]
  22. Collinet C, Rauzi M, Lenne PF, Lecuit T. 2015. Local and tissue-scale forces drive oriented junction growth during tissue extension. Nat. Cell Biol. 17:1247–58 [Google Scholar]
  23. Collins C, Nelson WJ. 2015. Running with neighbors: coordinating cell migration and cell-cell adhesion. Curr. Opin. Cell Biol. 36:62–70 [Google Scholar]
  24. Cooley J, Whitaker S, Sweeney S, Fraser S, Davidson B. 2011. Cytoskeletal polarity mediates localized induction of the heart progenitor lineage. Nat. Cell Biol. 13:952–57 [Google Scholar]
  25. Cota CD, Davidson B. 2015. Mitotic membrane turnover coordinates differential induction of the heart progenitor lineage. Dev. Cell 34:505–19 [Google Scholar]
  26. Davidson EH. 2010. Emerging properties of animal gene regulatory networks. Nature 468:911–20 [Google Scholar]
  27. Davidson EH, Levine MS. 2008. Properties of developmental gene regulatory networks. PNAS 105:20063–66 [Google Scholar]
  28. Davidson EH, Rast JP, Oliveri P, Ransick A, Calestani C. et al. 2002. A genomic regulatory network for development. Science 295:1669–78 [Google Scholar]
  29. Davidson LA, Marsden M, Keller R, Desimone DW. 2006. Integrin α5β1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension. Curr. Biol. 16:833–44 [Google Scholar]
  30. Dawes-Hoang RE, Parmar KM, Christiansen AE, Phelps CB, Brand AH, Wieschaus EF. 2005. folded gastrulation, cell shape change and the control of myosin localization. Development 132:4165–78 [Google Scholar]
  31. de Matos Simões S, Blankenship JT, Weitz O, Farrell DL, Tamada M. et al. 2010. Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation. Dev. Cell 19:377–88 [Google Scholar]
  32. Denker E, Bocina I, Jiang D. 2013. Tubulogenesis in a simple cell cord requires the formation of bi-apical cells through two discrete Par domains. Development 140:2985–96 [Google Scholar]
  33. Denker E, Jiang D. 2012. Ciona intestinalis notochord as a new model to investigate the cellular and molecular mechanisms of tubulogenesis. Semin. Cell Dev. Biol. 23:308–19 [Google Scholar]
  34. Denker E, Sehring IM, Dong B, Audisso J, Mathiesen B, Jiang D. 2015. Regulation by a TGFβ-ROCK-actomyosin axis secures a non-linear lumen expansion that is essential for tubulogenesis. Development 142:1639–50 [Google Scholar]
  35. Desplan C, Theis J, O'Farrell PH. 1985. The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Nature 318:630–35 [Google Scholar]
  36. Dohn MR, Mundell NA, Sawyer LM, Dunlap JA, Jessen JR. 2013. Planar cell polarity proteins differentially regulate extracellular matrix organization and assembly during zebrafish gastrulation. Dev. Biol. 383:39–51 [Google Scholar]
  37. Dona E, Barry JD, Valentin G, Quirin C, Khmelinskii A. et al. 2013. Directional tissue migration through a self-generated chemokine gradient. Nature 503:285–89 [Google Scholar]
  38. Doyle K, Hogan J, Lester M, Collier S. 2008. The Frizzled Planar Cell Polarity signaling pathway controls Drosophila wing topography. Dev. Biol. 317:354–67 [Google Scholar]
  39. Duchek P, Rorth P. 2001. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science 291:131–33 [Google Scholar]
  40. Duchek P, Somogyi K, Jekely G, Beccari S, Rorth P. 2001. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107:17–26 [Google Scholar]
  41. Duloquin L, Lhomond G, Gache C. 2007. Localized VEGF signaling from ectoderm to mesenchyme cells controls morphogenesis of the sea urchin embryo skeleton. Development 134:2293–302 [Google Scholar]
  42. Etienne-Manneville S. 2013. Microtubules in cell migration. Annu. Rev. Cell Dev. Biol. 29:471–99 [Google Scholar]
  43. Fort P, Theveneau E. 2014. PleiotRHOpic: Rho pathways are essential for all stages of neural crest development. Small GTPases 5:e27975 [Google Scholar]
  44. Fredriksson R, Schioth HB. 2005. The repertoire of G-protein-coupled receptors in fully sequenced genomes. Mol. Pharmacol. 67:1414–25 [Google Scholar]
  45. Futosi K, Fodor S, Mocsai A. 2013. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int. Immunopharmacol. 17:638–50 [Google Scholar]
  46. Gillingham AK, Sinka R, Torres IL, Lilley KS, Munro S. 2014. Toward a comprehensive map of the effectors of Rab GTPases. Dev. Cell 31:358–73 [Google Scholar]
  47. Gline S, Kaplan N, Bernadskaya Y, Abdu Y, Christiaen L. 2015. Surrounding tissues canalize motile cardiopharyngeal progenitors towards collective polarity and directed migration. Development 142:544–54 [Google Scholar]
  48. Grant BD, Donaldson JG. 2009. Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 10:597–608 [Google Scholar]
  49. Green RA, Kao HL, Audhya A, Arur S, Mayers JR. et al. 2011. A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. Cell 145:470–82 [Google Scholar]
  50. Gunsalus KC, Ge H, Schetter AJ, Goldberg DS, Han JD. et al. 2005. Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature 436:861–65 [Google Scholar]
  51. Gunsalus KC, Piano F. 2005. RNAi as a tool to study cell biology: building the genome-phenome bridge. Curr. Opin. Cell Biol. 17:3–8 [Google Scholar]
  52. Gunsalus KC, Rhrissorrakrai K. 2011. Networks in Caenorhabditis elegans. Curr. Opin. Genet. Dev. 21:787–98 [Google Scholar]
  53. Hashimoto H, Robin FB, Sherrard KM, Munro EM. 2015. Sequential contraction and exchange of apical junctions drives zippering and neural tube closure in a simple chordate. Dev. Cell 32:241–55 [Google Scholar]
  54. Herpin A, Fischer P, Liedtke D, Kluever N, Neuner C. et al. 2008. Sequential SDF1a and b-induced mobility guides Medaka PGC migration. Dev. Biol. 320:319–27 [Google Scholar]
  55. Houk AR, Jilkine A, Mejean CO, Boltyanskiy R, Dufresne ER. et al. 2012. Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148:175–88 [Google Scholar]
  56. Janssens K, Sung HH, Rorth P. 2010. Direct detection of guidance receptor activity during border cell migration. PNAS 107:7323–28 [Google Scholar]
  57. Jayo A, Parsons M. 2010. Fascin: a key regulator of cytoskeletal dynamics. Int. J. Biochem. Cell Biol. 42:1614–17 [Google Scholar]
  58. Jekely G, Sung HH, Luque CM, Rorth P. 2005. Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration. Dev. Cell 9:197–207 [Google Scholar]
  59. Jiang D, Munro EM, Smith WC. 2005. Ascidian prickle regulates both mediolateral and anterior-posterior cell polarity of notochord cells. Curr. Biol. 15:79–85 [Google Scholar]
  60. Jin T. 2011. GPCR-controlled chemotaxis in Dictyostelium discoideum. Wiley Interdiscip. Rev. Syst. Biol. Med. 3:717–27 [Google Scholar]
  61. Jones C, Qian D, Kim SM, Li S, Ren D. et al. 2014. Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene. diego and regulates coordinated cellular orientation in the mouse inner ear. Dev. Biol 395:62–72 [Google Scholar]
  62. José-Edwards DS, Oda-Ishii I, Kugler JE, Passamaneck YJ, Katikala L. et al. 2015. Brachyury, Foxa2 and the cis-regulatory origins of the notochord. PLOS Genet 11:e1005730 [Google Scholar]
  63. José-Edwards DS, Oda-Ishii I, Nibu Y, Di Gregorio A. 2013. Tbx2/3 is an essential mediator within the Brachyury gene network during Ciona notochord development. Development 140:2422–33 [Google Scholar]
  64. Julian L, Olson MF. 2014. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases 5:e29846 [Google Scholar]
  65. Katikala L, Aihara H, Passamaneck YJ, Gazdoiu S, José-Edwards DS. et al. 2013. Functional Brachyury binding sites establish a temporal read-out of gene expression in the Ciona notochord. PLOS Biol 11:e1001697 [Google Scholar]
  66. Kerridge S, Munjal A, Philippe JM, Jha A, de Las Bayonas AG. et al. 2016. Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis. Nat. Cell Biol. 18:3261–70 [Google Scholar]
  67. Klompstra D, Anderson DC, Yeh JY, Zilberman Y, Nance J. 2015. An instructive role for C.elegans E-cadherin in translating cell contact cues into cortical polarity. Nat. Cell Biol. 17:726–35 [Google Scholar]
  68. Kolsch V, Seher T, Fernandez-Ballester GJ, Serrano L, Leptin M. 2007. Control of Drosophila gastrulation by apical localization of adherens junctions and RhoGEF2. Science 315:384–86 [Google Scholar]
  69. Koorman T, Klompstra D, van der Voet M, Lemmens I, Ramalho JJ. et al. 2016. A combined binary interaction and phenotypic map of C.elegans cell polarity proteins. Nat. Cell Biol. 18:337–46 [Google Scholar]
  70. Ku CJ, Wang Y, Weiner OD, Altschuler SJ, Wu LF. 2012. Network crosstalk dynamically changes during neutrophil polarization. Cell 149:1073–83 [Google Scholar]
  71. Kulasingam V, Diamandis EP. 2013. Fascin-1 is a novel biomarker of aggressiveness in some carcinomas. BMC Med 11:53 [Google Scholar]
  72. Kunwar PS, Sano H, Renault AD, Barbosa V, Fuse N, Lehmann R. 2008. Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin. J. Cell Biol. 183:157–68 [Google Scholar]
  73. Lee JY, Harland RM. 2007. Actomyosin contractility and microtubules drive apical constriction in Xenopus bottle cells. Dev. Biol. 311:40–52 [Google Scholar]
  74. Llense F, Martin-Blanco E. 2008. JNK signaling controls border cell cluster integrity and collective cell migration. Curr. Biol. 18:538–44 [Google Scholar]
  75. Machacek M, Hodgson L, Welch C, Elliott H, Pertz O. et al. 2009. Coordination of Rho GTPase activities during cell protrusion. Nature 461:99–103 [Google Scholar]
  76. Majumder P, Aranjuez G, Amick J, McDonald JA. 2012. Par-1 controls myosin-II activity through myosin phosphatase to regulate border cell migration. Curr. Biol. 22:363–72 [Google Scholar]
  77. Mammoto A, Mammoto T, Ingber DE. 2012. Mechanosensitive mechanisms in transcriptional regulation. J. Cell Sci. 125:3061–73 [Google Scholar]
  78. Mammoto T, Mammoto A, Ingber DE. 2013. Mechanobiology and developmental control. Annu. Rev. Cell Dev. Biol. 29:27–61 [Google Scholar]
  79. Manning AJ, Peters KA, Peifer M, Rogers SL. 2013. Regulation of epithelial morphogenesis by the G protein–coupled receptor Mist and its ligand Fog. Sci. Signal. 6:ra98 [Google Scholar]
  80. Maritzen T, Schachtner H, Legler DF. 2015. On the move: endocytic trafficking in cell migration. Cell. Mol. Life Sci. 72:2119–34 [Google Scholar]
  81. Martin AC, Goldstein B. 2014. Apical constriction: themes and variations on a cellular mechanism driving morphogenesis. Development 141:1987–98 [Google Scholar]
  82. Martin AC, Kaschube M, Wieschaus EF. 2009. Pulsed contractions of an actin-myosin network drive apical constriction. Nature 457:495–99 [Google Scholar]
  83. Mathew SJ, Rembold M, Leptin M. 2011. Role for Traf4 in polarizing adherens junctions as a prerequisite for efficient cell shape changes. Mol. Cell. Biol. 31:4978–93 [Google Scholar]
  84. McDonald JA, Khodyakova A, Aranjuez G, Dudley C, Montell DJ. 2008. PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells. Curr. Biol. 18:1659–67 [Google Scholar]
  85. McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ. 1984. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature 308:428–33 [Google Scholar]
  86. Mohr SE, Smith JA, Shamu CE, Neumuller RA, Perrimon N. 2014. RNAi screening comes of age: improved techniques and complementary approaches. Nat. Rev. Mol. Cell Biol. 15:591–600 [Google Scholar]
  87. Montell DJ. 2008. Morphogenetic cell movements: diversity from modular mechanical properties. Science 322:1502–5 [Google Scholar]
  88. Montell DJ, Rorth P, Spradling AC. 1992. slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C/EBP. Cell 71:51–62 [Google Scholar]
  89. Montell DJ, Yoon WH, Starz-Gaiano M. 2012. Group choreography: mechanisms orchestrating the collective movement of border cells. Nat. Rev. Mol. Cell Biol. 13:631–45 [Google Scholar]
  90. Munjal A, Philippe JM, Munro E, Lecuit T. 2015. A self-organized biomechanical network drives shape changes during tissue morphogenesis. Nature 524:351–55 [Google Scholar]
  91. Murphy AM, Montell DJ. 1996. Cell type–specific roles for Cdc42, Rac, and RhoL in Drosophila oogenesis. J. Cell Biol. 133:617–30 [Google Scholar]
  92. Nance J. 2014. Getting to know your neighbor: cell polarization in early embryos. J. Cell Biol. 206:823–32 [Google Scholar]
  93. Nance J, Zallen JA. 2011. Elaborating polarity: PAR proteins and the cytoskeleton. Development 138:799–809 [Google Scholar]
  94. Nelson MD, Zhou E, Kiontke K, Fradin H, Maldonado G. et al. 2011. A bow-tie genetic architecture for morphogenesis suggested by a genome-wide RNAi screen in Caenorhabditis elegans. PLOS Genet 7:e1002010 [Google Scholar]
  95. Newman-Smith E, Kourakis MJ, Reeves W, Veeman M, Smith WC. 2015. Reciprocal and dynamic polarization of planar cell polarity core components and myosin. eLife 4:e05361 [Google Scholar]
  96. Nieto MA, Sargent MG, Wilkinson DG, Cooke J. 1994. Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 264:835–39 [Google Scholar]
  97. Nir O, Bakal C, Perrimon N, Berger B. 2010. Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen. Genome Res 20:372–80 [Google Scholar]
  98. Norton J, Cooley J, Islam AF, Cota CD, Davidson B. 2013. Matrix adhesion polarizes heart progenitor induction in the invertebrate chordate Ciona intestinalis. Development 140:1301–11 [Google Scholar]
  99. Nüsslein-Volhard C, Wieschaus E. 1980. Mutations affecting segment number and polarity in Drosophila. Nature 287:795–801 [Google Scholar]
  100. Pare AC, Vichas A, Fincher CT, Mirman Z, Farrell DL. et al. 2014. A positional Toll receptor code directs convergent extension in Drosophila. Nature 515:523–27 [Google Scholar]
  101. Paul NR, Jacquemet G, Caswell PT. 2015. Endocytic trafficking of integrins in cell migration. Curr. Biol. 25:R1092–105 [Google Scholar]
  102. Perez-Alcala S, Nieto MA, Barbas JA. 2004. LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest. Development 131:4455–65 [Google Scholar]
  103. Peter IS, Davidson EH. 2011. A gene regulatory network controlling the embryonic specification of endoderm. Nature 474:635–39 [Google Scholar]
  104. Piloto S, Schilling TF. 2010. Ovo1 links Wnt signaling with N-cadherin localization during neural crest migration. Development 137:1981–90 [Google Scholar]
  105. Pinheiro EM, Montell DJ. 2004. Requirement for Par-6 and Bazooka in Drosophila border cell migration. Development 131:5243–51 [Google Scholar]
  106. Pollard TD, Borisy GG. 2003. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112:453–65 [Google Scholar]
  107. Poukkula M, Cliffe A, Changede R, Rorth P. 2011. Cell behaviors regulated by guidance cues in collective migration of border cells. J. Cell Biol. 192:513–24 [Google Scholar]
  108. Prasad M, Montell DJ. 2007. Cellular and molecular mechanisms of border cell migration analyzed using time-lapse live-cell imaging. Dev. Cell 12:997–1005 [Google Scholar]
  109. Rafiq K, Shashikant T, McManus CJ, Ettensohn CA. 2014. Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins. Development 141:950–61 [Google Scholar]
  110. Ragkousi K, Beh J, Sweeney S, Starobinska E, Davidson B. 2011. A single GATA factor plays discrete, lineage specific roles in ascidian heart development. Dev. Biol. 352:154–63 [Google Scholar]
  111. Rauzi M, Lenne PF, Lecuit T. 2010. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468:1110–14 [Google Scholar]
  112. Rauzi M, Verant P, Lecuit T, Lenne PF. 2008. Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis. Nat. Cell Biol. 10:1401–10 [Google Scholar]
  113. Reddien PW, Horvitz HR. 2000. CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat. Cell Biol. 2:131–36 [Google Scholar]
  114. Reig G, Pulgar E, Concha ML. 2014. Cell migration: from tissue culture to embryos. Development 141:1999–2013 [Google Scholar]
  115. Revenu C, Gilmour D. 2009. EMT 2.0: shaping epithelia through collective migration. Curr. Opin. Genet. Dev. 19:338–42 [Google Scholar]
  116. Richardson BE, Lehmann R. 2010. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat. Rev. Mol. Cell Biol. 11:37–49 [Google Scholar]
  117. Ridley AJ. 2011. Life at the leading edge. Cell 145:1012–22 [Google Scholar]
  118. Ridley AJ. 2015. Rho GTPase signalling in cell migration. Curr. Opin. Cell Biol. 36:103–12 [Google Scholar]
  119. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH. et al. 2003. Cell migration: integrating signals from front to back. Science 302:1704–9 [Google Scholar]
  120. Roh-Johnson M, Shemer G, Higgins CD, McClellan JH, Werts AD. et al. 2012. Triggering a cell shape change by exploiting preexisting actomyosin contractions. Science 335:1232–35 [Google Scholar]
  121. Rottinger E, Saudemont A, Duboc V, Besnardeau L, McClay D, Lepage T. 2008. FGF signals guide migration of mesenchymal cells, control skeletal morphogenesis and regulate gastrulation during sea urchin development. Development 135:353–65 [Google Scholar]
  122. Saunders LR, McClay DR. 2014. Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition. Development 141:1503–13 [Google Scholar]
  123. Scarpa E, Mayor R. 2016. Collective cell migration in development. J. Cell Biol. 212:143–55 [Google Scholar]
  124. Scarpa E, Szabo A, Bibonne A, Theveneau E, Parsons M, Mayor R. 2015. Cadherin switch during EMT in neural crest cells leads to contact inhibition of locomotion via repolarization of forces. Dev. Cell 34:421–34 [Google Scholar]
  125. Schwarz EM, Kato M, Sternberg PW. 2012. Functional transcriptomics of a migrating cell in Caenorhabditis elegans. PNAS 109:16246–51 [Google Scholar]
  126. Sehring IM, Dong B, Denker E, Bhattachan P, Deng W. et al. 2014. An equatorial contractile mechanism drives cell elongation but not cell division. PLOS Biol 12:e1001781 [Google Scholar]
  127. Sehring IM, Recho P, Denker E, Kourakis M, Mathiesen B. et al. 2015. Assembly and positioning of actomyosin rings by contractility and planar cell polarity. eLife 4:e09206 [Google Scholar]
  128. Shekhar S, Pernier J, Carlier MF. 2016. Regulators of actin filament barbed ends at a glance. J. Cell Sci. 129:1085–91 [Google Scholar]
  129. Sherrard K, Robin F, Lemaire P, Munro E. 2010. Sequential activation of apical and basolateral contractility drives ascidian endoderm invagination. Curr. Biol. 20:1499–510 [Google Scholar]
  130. Shi W, Peyrot SM, Munro E, Levine M. 2009. FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. Development 136:23–28 [Google Scholar]
  131. Simões-Costa M, Bronner ME. 2015. Establishing neural crest identity: a gene regulatory recipe. Development 142:242–57 [Google Scholar]
  132. Simões-Costa M, Tan-Cabugao J, Antoshechkin I, Sauka-Spengler T, Bronner ME. 2014. Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory network. Genome Res 24:281–90 [Google Scholar]
  133. Sonnichsen B, Koski LB, Walsh A, Marschall P, Neumann B. et al. 2005. Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434:462–69 [Google Scholar]
  134. Stathopoulos A, Van Drenth M, Erives A, Markstein M, Levine M. 2002. Whole-genome analysis of dorsal-ventral patterning in the Drosophila embryo. Cell 111:687–701 [Google Scholar]
  135. Stewart AL, Young HM, Popoff M, Anderson RB. 2007. Effects of pharmacological inhibition of small GTPases on axon extension and migration of enteric neural crest–derived cells. Dev. Biol. 307:92–104 [Google Scholar]
  136. Takahashi H, Hotta K, Erives A, Di Gregorio A, Zeller RW. et al. 1999. Brachyury downstream notochord differentiation in the ascidian embryo. Genes Dev 13:1519–23 [Google Scholar]
  137. Takeichi M. 1995. Morphogenetic roles of classic cadherins. Curr. Opin. Cell Biol. 7:619–27 [Google Scholar]
  138. Tan VY, Lewis SJ, Adams JC, Martin RM. 2013. Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis. BMC Med 11:52 [Google Scholar]
  139. Tanegashima K, Zhao H, Dawid IB. 2008. WGEF activates Rho in the Wnt-PCP pathway and controls convergent extension in Xenopus gastrulation. EMBO J 27:606–17 [Google Scholar]
  140. Tarbashevich K, Raz E. 2010. The nuts and bolts of germ-cell migration. Curr. Opin. Cell Biol. 22:715–21 [Google Scholar]
  141. Theveneau E, Marchant L, Kuriyama S, Gull M, Moepps B. et al. 2010. Collective chemotaxis requires contact-dependent cell polarity. Dev. Cell 19:39–53 [Google Scholar]
  142. Theveneau E, Mayor R. 2013. Collective cell migration of epithelial and mesenchymal cells. Cell. Mol. Life Sci. 70:3481–92 [Google Scholar]
  143. Thiery JP, Acloque H, Huang RY, Nieto MA. 2009. Epithelial-mesenchymal transitions in development and disease. Cell 139:871–90 [Google Scholar]
  144. Venkiteswaran G, Lewellis SW, Wang J, Reynolds E, Nicholson C, Knaut H. 2013. Generation and dynamics of an endogenous, self-generated signaling gradient across a migrating tissue. Cell 155:674–87 [Google Scholar]
  145. Vicente-Manzanares M, Webb DJ, Horwitz AR. 2005. Cell migration at a glance. J. Cell Sci. 118:4917–19 [Google Scholar]
  146. Wagner GP, Pavlicev M, Cheverud JM. 2007. The road to modularity. Nat. Rev. Genet. 8:921–31 [Google Scholar]
  147. Wang F, Dumstrei K, Haag T, Hartenstein V. 2004. The role of DE-cadherin during cellularization, germ layer formation and early neurogenesis in the Drosophila embryo. Dev. Biol. 270:350–63 [Google Scholar]
  148. Wang X, Adam JC, Montell D. 2007. Spatially localized Kuzbanian required for specific activation of Notch during border cell migration. Dev. Biol. 301:532–40 [Google Scholar]
  149. Wang X, Bo J, Bridges T, Dugan KD, Pan TC. et al. 2006. Analysis of cell migration using whole-genome expression profiling of migratory cells in the Drosophila ovary. Dev. Cell 10:483–95 [Google Scholar]
  150. Wang X, He L, Wu YI, Hahn KM, Montell DJ. 2010. Light-mediated activation reveals a key role for Rac in collective guidance of cell movement in vivo. Nat. Cell Biol. 12:591–97 [Google Scholar]
  151. Wu SY, McClay DR. 2007. The Snail repressor is required for PMC ingression in the sea urchin embryo. Development 134:1061–70 [Google Scholar]
  152. Yam PT, Wilson CA, Ji L, Hebert B, Barnhart EL. et al. 2007. Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J. Cell Biol. 178:1207–21 [Google Scholar]
  153. Yang HW, Collins SR, Meyer T. 2016. Locally excitable Cdc42 signals steer cells during chemotaxis. Nat. Cell Biol. 18:191–201 [Google Scholar]
  154. Zaidel-Bar R, Itzkovitz S, Ma'ayan A, Iyengar R, Geiger B. 2007. Functional atlas of the integrin adhesome. Nat. Cell Biol. 9:858–67 [Google Scholar]
  155. Zallen JA, Wieschaus E. 2004. Patterned gene expression directs bipolar planar polarity in Drosophila. Dev. Cell 6:343–55 [Google Scholar]
  156. Zamir E, Geiger B. 2001. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114:3583–90 [Google Scholar]
  157. Zeitlinger J, Zinzen RP, Stark A, Kellis M, Zhang H. et al. 2007. Whole-genome ChIP-chip analysis of Dorsal, Twist, and Snail suggests integration of diverse patterning processes in the Drosophila embryo. Genes Dev 21:385–90 [Google Scholar]
  158. Zhen Y, Stenmark H. 2015. Cellular functions of Rab GTPases at a glance. J. Cell Sci. 128:3171–76 [Google Scholar]

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