Skip to main content
Log in

Cell segregation in the vertebrate hindbrain: a matter of boundaries

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Segregating cells into compartments during embryonic development is essential for growth and pattern formation. In the developing hindbrain, boundaries separate molecularly, physically and neuroanatomically distinct segments called rhombomeres. After rhombomeric cells have acquired their identity, interhombomeric boundaries restrict cell intermingling between adjacent rhombomeres and act as signaling centers to pattern the surrounding tissue. Several works have stressed the relevance of Eph/ephrin signaling in rhombomeric cell sorting. Recent data have unveiled the role of this pathway in the assembly of actomyosin cables as an important mechanism for keeping cells from different rhombomeres segregated. In this Review, we will provide a short summary of recent evidences gathered in different systems suggesting that physical actomyosin barriers can be a general mechanism for tissue separation. We will discuss current evidences supporting a model where cell–cell signaling pathways, such as Eph/ephrin, govern compartmental cell sorting through modulation of the actomyosin cytoskeleton and cell adhesive properties to prevent cell intermingling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ADAM10:

A disintegrin and metalloproteinase domain-containing protein 10

AP:

Anteroposterior

DV:

Dorsoventral

CNS:

Central nervous system

Cadh2:

Cadherin 2

Cyp26:

Cytochrome p450 family 26 enzymes

EphA4MO/ephrinB2Amo:

EphA4/ephrinB2a-morphants

FGF:

Fibroblast growth factor

GEFs:

Guanine nucleotide exchange factors

GAPs:

GTPase-activating proteins

HoxPG1:

Hox paralogous group 1 genes

MHB:

Mid-hindbrain boundary

RA:

Retinoic acid

References

  1. Garcia-Bellido A, Ripoll P, Morata G (1973) Developmental compartmentalisation of the wing disk of Drosophila. Nature New Biol 245:251–253

    Article  CAS  PubMed  Google Scholar 

  2. Morata G, Lawrence PA (1978) Anterior and posterior compartments in the head of Drosophila. Nature 274:473–474

    Article  CAS  PubMed  Google Scholar 

  3. Lawrence PA, Struhl G, Morata G (1979) Bristle patterns and compartment boundaries in the tarsi of Drosophila. J Embryol Exp Morphol 51:195–208

    CAS  PubMed  Google Scholar 

  4. Sanson B (2001) Generating patterns from fields of cells. Examples from Drosophila segmentation. EMBO Rep 2:1083–1088. doi:10.1093/embo-reports/kve255

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Rohani N, Canty L, Luu O et al (2011) EphrinB/EphB signaling controls embryonic germ layer separation by contact-induced cell detachment. PLoS Biol 9:e1000597. doi:10.1371/journal.pbio.1000597.g009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Reintsch WE, Habring-Mueller A, Wang RW et al (2005) beta-Catenin controls cell sorting at the notochord-somite boundary independently of cadherin-mediated adhesion. J Cell Biol 170:675–686. doi:10.1083/jcb.200503009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Moens CB, Cordes SP, Giorgianni MW et al (1998) Equivalence in the genetic control of hindbrain segmentation in fish and mouse. Development 125:381–391

    CAS  PubMed  Google Scholar 

  8. Tümpel S, Wiedemann LM, Krumlauf R (2009) Hox genes and segmentation of the vertebrate hindbrain. Curr Top Dev Biol 88:103–137. doi:10.1016/S0070-2153(09)88004-6

    Article  PubMed  CAS  Google Scholar 

  9. Stern CD, Keynes RJ (1987) Interactions between somite cells: the formation and maintenance of segment boundaries in the chick embryo. Development 99:261–272

    CAS  PubMed  Google Scholar 

  10. Dahmann C, Oates AC, Brand M (2011) Boundary formation and maintenance in tissue development. Nat Rev Genet 12:43–55. doi:10.1038/nrg2902

    Article  CAS  PubMed  Google Scholar 

  11. Xu Q, Wilkinson DG (2013) Boundary formation in the development of the vertebrate hindbrain. Wiley Interdiscip Rev Dev Biol 2:735–745. doi:10.1002/wdev.106

    Article  CAS  PubMed  Google Scholar 

  12. Fagotto F (2014) The cellular basis of tissue separation. Development 141:3303–3318. doi:10.1242/dev.090332

    Article  CAS  PubMed  Google Scholar 

  13. Munjal A, Lecuit T (2014) Actomyosin networks and tissue morphogenesis. Development 141:1789–1793. doi:10.1242/dev.091645

    Article  CAS  PubMed  Google Scholar 

  14. Zecca M, Struhl G (2002) Subdivision of the Drosophila wing imaginal disc by EGFR-mediated signaling. Development 129:1357–1368

    CAS  PubMed  Google Scholar 

  15. Tepass U, Godt D, Winklbauer R (2002) Cell sorting in animal development: signalling and adhesive mechanisms in the formation of tissue boundaries. Curr Opin Genet Dev 12:572–582

    Article  CAS  PubMed  Google Scholar 

  16. Tremblay KD, Zaret KS (2005) Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Dev Biol 280:87–99. doi:10.1016/j.ydbio.2005.01.003

    Article  CAS  PubMed  Google Scholar 

  17. Langenberg T, Dracz T, Oates AC et al (2006) Analysis and visualization of cell movement in the developing zebrafish brain. Dev Dyn 235:928–933. doi:10.1002/dvdy.20692

    Article  PubMed  Google Scholar 

  18. Calzolari S, Terriente J, Pujades C (2014) Cell segregation in the vertebrate hindbrain relies on actomyosin cables located at the interhombomeric boundaries. EMBO J 33:686–701. doi:10.1002/embj.201386003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Monier B, Pélissier-Monier A, Brand AH, Sanson B (2010) An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos. Nat Cell Biol 12:60–5–sup:1–9. doi:10.1038/ncb2005

  20. Major RJ, Irvine KD (2005) Influence of Notch on dorsoventral compartmentalization and actin organization in the Drosophila wing. Development 132:3823–3833. doi:10.1242/dev.01957

    Article  CAS  PubMed  Google Scholar 

  21. Major RJ, Irvine KD (2006) Localization and requirement for Myosin II at the dorsal-ventral compartment boundary of the Drosophila wing. Dev Dyn 235:3051–3058. doi:10.1002/dvdy.20966

    Article  CAS  PubMed  Google Scholar 

  22. Landsberg KP, Farhadifar R, Ranft J et al (2009) Increased cell bond tension governs cell sorting at the drosophila anteroposterior compartment boundary. Curr Biol 19:1950–1955. doi:10.1016/j.cub.2009.10.021

    Article  CAS  PubMed  Google Scholar 

  23. Becam I, Rafel N, Hong X et al (2011) Notch-mediated repression of bantam miRNA contributes to boundary formation in the Drosophila wing. Development 138:3781–3789. doi:10.1242/dev.064774

    Article  CAS  PubMed  Google Scholar 

  24. Curt JR, de Navas LF, Sánchez-Herrero E (2013) Differential activity of Drosophila Hox Genes induces myosin expression and can maintain compartment boundaries. PLoS One 8:e57159. doi:10.1371/journal.pone.0057159.t001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Rohani N, Parmeggiani A, Winklbauer R, Fagotto F (2014) Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation. PLoS Biol 12:e1001955. doi:10.1371/journal.pbio.1001955.s016

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Fagotto F, Rohani N, Touret A-S, Li R (2013) A molecular base for cell sorting at embryonic boundaries: contact inhibition of cadherin adhesion by ephrin/Eph-dependent contractility. Dev Cell. doi:10.1016/j.devcel.2013.09.004

    Google Scholar 

  27. Moens CB, Prince VE (2002) Constructing the hindbrain: insights from the zebrafish. Dev Dyn 224:1–17. doi:10.1002/dvdy.10086

    Article  PubMed  Google Scholar 

  28. Kiecker C, Lumsden A (2005) Compartments and their boundaries in vertebrate brain development. Nat Rev Neurosci 6:553–564. doi:10.1038/nrn1702

    Article  CAS  PubMed  Google Scholar 

  29. Bulfone A, Puelles L, Porteus MH et al (1993) Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. J Neurosci 13:3155–3172

    CAS  PubMed  Google Scholar 

  30. Alvarado-Mallart RM, Martinez S, Lance-Jones CC (1990) Pluripotentiality of the 2-day-old avian germinative neuroepithelium. Dev Biol 139:75–88

    Article  CAS  PubMed  Google Scholar 

  31. Liu A, Joyner AL (2001) EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development 128:181–191

    CAS  PubMed  Google Scholar 

  32. Martinez S, Wassef M, Alvarado-Mallart RM (1991) Induction of a mesencephalic phenotype in the 2-day-old chick prosencephalon is preceded by the early expression of the homeobox gene en. Neuron 6:971–981

    Article  CAS  PubMed  Google Scholar 

  33. Murakami Y, Uchida K, Rijli FM, Kuratani S (2005) Evolution of the brain developmental plan: insights from agnathans. Developmental Biology 280:249–259. doi:10.1016/j.ydbio.2005.02.008

    Article  CAS  PubMed  Google Scholar 

  34. Guthrie S (2007) Patterning and axon guidance of cranial motor neurons. Nat Rev Neurosci 8:859–871. doi:10.1038/nrn2254

    Article  CAS  PubMed  Google Scholar 

  35. Fraser SE, Keynes R, Lumsden A (1990) Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions. Nature 344:431–434

    Article  CAS  PubMed  Google Scholar 

  36. Jimenez-Guri E, Udina F, Colas J-F et al (2010) Clonal analysis in mice underlines the importance of rhombomeric boundaries in cell movement restriction during hindbrain segmentation. PLoS One 5:e10112. doi:10.1371/journal.pone.0010112

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Irving C, Mason I (2000) Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. Development 127:177–186

    CAS  PubMed  Google Scholar 

  38. McKay IJ, Muchamore I, Krumlauf R et al (1994) The kreisler mouse: a hindbrain segmentation mutant that lacks two rhombomeres. Development 120:2199–2211

    CAS  PubMed  Google Scholar 

  39. Walshe J, Maroon H, McGonnell IM et al (2002) Establishment of hindbrain segmental identity requires signaling by FGF3 and FGF8. Curr Biol 12:1117–1123

    Article  CAS  PubMed  Google Scholar 

  40. Maves L, Jackman W, Kimmel CB (2002) FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain. Development 129:3825–3837

    CAS  PubMed  Google Scholar 

  41. Wiellette EL (2003) vhnf1 and Fgf signals synergize to specify rhombomere identity in the zebrafish hindbrain. Development 130:3821–3829. doi:10.1242/dev.00572

    Article  CAS  PubMed  Google Scholar 

  42. Aragon F, Pujades C (2009) FGF signaling controls caudal hindbrain specification through Ras-ERK1/2 pathway. BMC Dev Biol 9:61. doi:10.1186/1471-213X-9-61

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  43. Hernandez R, Rikhof HA, Bachmann R, Moens CB (2004) vhnf1 integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish. Development 131:4511–4520. doi:10.1242/dev.01297

    Article  CAS  PubMed  Google Scholar 

  44. Aragon F, Vázquez-Echeverría C, Ulloa E et al (2005) vHnf1 regulates specification of caudal rhombomere identity in the chick hindbrain. Dev Dyn 234:567–576. doi:10.1002/dvdy.20528

    Article  CAS  PubMed  Google Scholar 

  45. Labalette C, Bouchoucha YX, Wassef MA et al (2010) Hindbrain patterning requires fine-tuning of early krox20 transcription by Sprouty 4. Development 138:317–326. doi:10.1242/dev.057299

    Article  CAS  Google Scholar 

  46. Morriss-Kay GM, Murphy P, Hill RE, Davidson DR (1991) Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. EMBO J 10:2985–2995

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Pasqualetti M, Neun R, Davenne M, Rijli FM (2001) Retinoic acid rescues inner ear defects in Hoxa1 deficient mice. Nat Genet 29:34–39. doi:10.1038/ng702

    Article  CAS  PubMed  Google Scholar 

  48. Glover JC, Renaud J-S, Rijli FM (2006) Retinoic acid and hindbrain patterning. J Neurobiol 66:705–725. doi:10.1002/neu.20272

    Article  CAS  PubMed  Google Scholar 

  49. Sirbu IO, Gresh L, Barra J, Duester G (2005) Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression. Development 132:2611–2622. doi:10.1242/dev.01845

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Hernandez RE, Putzke AP, Myers JP et al (2007) Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development. Development 134:177–187. doi:10.1242/dev.02706

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. White RJ, Nie Q, Lander AD, Schilling TF (2007) Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the Zebrafish embryo. PLoS Biol 5:e304. doi:10.1371/journal.pbio.0050304.sg003

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Lecaudey V, Anselme I, Rosa F, Schneider-Maunoury S (2004) The zebrafish Iroquois gene iro7 positions the r4/r5 boundary and controls neurogenesis in the rostral hindbrain. Development 131:3121–3131. doi:10.1242/dev.01190

    Article  CAS  PubMed  Google Scholar 

  53. Rossel M, Capecchi MR (1999) Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development 126:5027–5040

    CAS  PubMed  Google Scholar 

  54. Barrow JR, Stadler HS, Capecchi MR (2000) Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127:933–944

    CAS  PubMed  Google Scholar 

  55. McNulty CL, Peres JN, Bardine N et al (2005) Knockdown of the complete Hox paralogous group 1 leads to dramatic hindbrain and neural crest defects. Development 132:2861–2871. doi:10.1242/dev.01872

    Article  CAS  PubMed  Google Scholar 

  56. Wassef MA, Chomette D, Pouilhe M et al (2008) Rostral hindbrain patterning involves the direct activation of a Krox20 transcriptional enhancer by Hox/Pbx and Meis factors. Development 135:3369–3378. doi:10.1242/dev.023614

    Article  CAS  PubMed  Google Scholar 

  57. Makki N, Capecchi MR (2010) Hoxa1 lineage tracing indicates a direct role for Hoxa1 in the development of the inner ear, the heart, and the third rhombomere. Dev Biol 341:499–509. doi:10.1016/j.ydbio.2010.02.014

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Alexander T, Nolte C, Krumlauf R (2009) Hox genes and segmentation of the hindbrain and axial skeleton. Annu Rev Cell Dev Biol 25:431–456. doi:10.1146/annurev.cellbio.042308.113423

    Article  CAS  PubMed  Google Scholar 

  59. Schneider-Maunoury S, Topilko P, Seitandou T et al (1993) Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell 75:1199–1214

    Article  CAS  PubMed  Google Scholar 

  60. Schneider-Maunoury S, Seitanidou T, Charnay P, Lumsden A (1997) Segmental and neuronal architecture of the hindbrain of Krox-20 mouse mutants. Development 124:1215–1226

    CAS  PubMed  Google Scholar 

  61. Voiculescu O, Taillebourg E, Pujades C et al (2001) Hindbrain patterning: Krox20 couples segmentation and specification of regional identity. Development 128:4967–4978

    CAS  PubMed  Google Scholar 

  62. Helmbacher F, Pujades C, Desmarquet C et al (1998) Hoxa1 and Krox-20 synergize to control the development of rhombomere 3. Development 125:4739–4748

    CAS  PubMed  Google Scholar 

  63. Moens CB, Yan YL, Appel B et al (1996) valentino: a zebrafish gene required for normal hindbrain segmentation. Development 122:3981–3990

    CAS  PubMed  Google Scholar 

  64. Lumsden A, Keynes R (1989) Segmental patterns of neuronal development in the chick hindbrain. Nature 337:424–428. doi:10.1038/337424a0

    Article  CAS  PubMed  Google Scholar 

  65. Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274:1109–1115

    Article  CAS  PubMed  Google Scholar 

  66. Jimenez-Guri E, Pujades C (2011) An ancient mechanism of hindbrain patterning has been conserved in vertebrate evolution. Evol Dev 13:38–46. doi:10.1111/j.1525-142X.2010.00454.x

    Article  CAS  PubMed  Google Scholar 

  67. Xu Q, Mellitzer G, Robinson V, Wilkinson DG (1999) In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399:267–271. doi:10.1038/20452

    Article  CAS  PubMed  Google Scholar 

  68. Cooke JE, Kemp HA, Moens CB (2005) EphA4 is required for cell adhesion and rhombomere-boundary formation in the Zebrafish. Curr Biol 15:536–542. doi:10.1016/j.cub.2005.02.019

    Article  CAS  PubMed  Google Scholar 

  69. Kemp HA, Cooke JE, Moens CB (2009) EphA4 and EfnB2a maintain rhombomere coherence by independently regulating intercalation of progenitor cells in the zebrafish neural keel. Dev Biol 327:313–326. doi:10.1016/j.ydbio.2008.12.010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Schilling TF, Prince V, Ingham PW (2001) Plasticity in zebrafish hox expression in the hindbrain and cranial neural crest. Dev Biol 231:201–216. doi:10.1006/dbio.2000.9997

    Article  CAS  PubMed  Google Scholar 

  71. Zhang C, Frazier JM, Chen H et al (2014) Molecular and morphological changes in zebrafish following transient ethanol exposure during defined developmental stages. Neurotoxicol Teratol 44:1–11. doi:10.1016/j.ntt.2014.06.001

    Article  CAS  Google Scholar 

  72. Gutzman JH, Sive H (2010) Epithelial relaxation mediated by the myosin phosphatase regulator Mypt1 is required for brain ventricle lumen expansion and hindbrain morphogenesis. Development 137:795–804. doi:10.1242/dev.042705

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Guthrie S, Lumsden A (1991) Formation and regeneration of rhombomere boundaries in the developing chick hindbrain. Development 112:221–229

    CAS  PubMed  Google Scholar 

  74. Riley BB, Chiang M-Y, Storch EM et al (2004) Rhombomere boundaries are Wnt signaling centers that regulate metameric patterning in the zebrafish hindbrain. Dev Dyn 231:278–291. doi:10.1002/dvdy.20133

    Article  CAS  PubMed  Google Scholar 

  75. Terriente J, Gerety SS, Watanabe-Asaka T et al (2012) Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis. Development 139:2978–2987. doi:10.1242/dev.080135

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Sela-Donenfeld D, Kayam G, Wilkinson DG (2009) Boundary cells regulate a switch in the expression of FGF3 in hindbrain rhombomeres. BMC Dev Biol 9:16. doi:10.1186/1471-213X-9-16

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  77. Prin F, Serpente P, Itasaki N, Gould AP (2014) Hox proteins drive cell segregation and non-autonomous apical remodelling during hindbrain segmentation. Development. doi:10.1242/dev.098954

    PubMed Central  PubMed  Google Scholar 

  78. Cheng Y-C, Amoyel M, Qiu X et al (2004) Notch activation regulates the segregation and differentiation of rhombomere boundary cells in the zebrafish hindbrain. Dev Cell 6:539–550

    Article  CAS  PubMed  Google Scholar 

  79. Theil T, Ariza-McNaughton L, Manzanares M et al (2002) Requirement for downregulation of kreisler during late patterning of the hindbrain. Development 129:1477–1485

    CAS  PubMed  Google Scholar 

  80. Nieto MA, Gilardi-Hebenstreit P, Charnay P, Wilkinson DG (1992) A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm. Development 116:1137–1150

    CAS  PubMed  Google Scholar 

  81. Becker N, Gilardi-Hebenstreit P, Seitanidou T et al (1995) Characterisation of the Sek-1 receptor tyrosine kinase. FEBS Lett 368:353–357

    Article  CAS  PubMed  Google Scholar 

  82. Cooke J, Moens C, Roth L et al (2001) Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain. Development 128:571–580

    CAS  PubMed  Google Scholar 

  83. Pasquale EB (2008) Eph-ephrin bidirectional signaling in physiology and disease. Cell 133:38–52. doi:10.1016/j.cell.2008.03.011

    Article  CAS  PubMed  Google Scholar 

  84. Himanen JP, Yermekbayeva L, Janes PW et al (2010) Architecture of Eph receptor clusters. Proc Natl Acad Sci 107:10860–10865. doi:10.1073/pnas.1004148107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Poliakov A, Cotrina M, Wilkinson DG (2004) Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly. Dev Cell 7:465–480. doi:10.1016/j.devcel.2004.09.006

    Article  CAS  PubMed  Google Scholar 

  86. Noren NK, Pasquale EB (2007) Paradoxes of the EphB4 receptor in cancer. Cancer Res 67:3994–3997. doi:10.1158/0008-5472.CAN-07-0525

    Article  CAS  PubMed  Google Scholar 

  87. Egea J, Klein R (2007) Bidirectional Eph-ephrin signaling during axon guidance. Trends Cell Biol 17:230–238. doi:10.1016/j.tcb.2007.03.004

    Article  CAS  PubMed  Google Scholar 

  88. Pitulescu ME, Adams RH (2010) Eph/ephrin molecules–a hub for signaling and endocytosis. Genes Dev 24:2480–2492. doi:10.1101/gad.1973910

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Cayuso J, Xu Q, Wilkinson DG (2014) Mechanisms of boundary formation by Eph receptor and ephrin signaling. Dev Biol 401:122–131. doi:10.1016/j.ydbio.2014.11.013

  90. Martz E, Phillips HM, Steinberg MS (1974) Contact inhibition of overlapping and differential cell adhesion: a sufficient model for the control of certain cell culture morphologies. J Cell Sci 16:401–419

    CAS  PubMed  Google Scholar 

  91. Solanas G, Cortina C, Sevillano M, Batlle E (2011) Cleavage of E-cadherin by ADAM10 mediates epithelial cell sorting downstream of EphB signalling. Nat Cell Biol 13:1100–1107. doi:10.1038/ncb2298

    Article  CAS  PubMed  Google Scholar 

  92. Stockinger P, Maitre JL, Heisenberg CP (2011) Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube. Development 138:4673–4683. doi:10.1242/dev.071233

    Article  CAS  PubMed  Google Scholar 

  93. Julich D, Mould AP, Koper E, Holley SA (2009) Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling. Development 136:2913–2921. doi:10.1242/dev.038935

    Article  CAS  PubMed  Google Scholar 

  94. Jørgensen C, Sherman A, Chen GI et al (2009) Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells. Science 326:1502–1509. doi:10.1126/science.1176615

    Article  PubMed  CAS  Google Scholar 

  95. Klein R (2012) Eph/ephrin signalling during development. Development 139:4105–4109. doi:10.1242/dev.074997

    Article  CAS  PubMed  Google Scholar 

  96. Defourny J, Poirrier A-L, Lallemend FCO et al. (1AD) Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells. Nat Commun 4:1438. doi: 10.1038/ncomms2445

  97. Yamazaki T, Masuda J, Omori T et al (2009) EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility. J Cell Sci 122:243–255. doi:10.1242/jcs.036467

    Article  CAS  PubMed  Google Scholar 

  98. Boissier P, Chen J, Huynh-Do U (2013) EphA2 signaling following endocytosis: role of Tiam1. Traffic 14:1255–1271. doi:10.1111/tra.12123

    Article  CAS  PubMed  Google Scholar 

  99. Cowan CW, Shao YR, Sahin M et al (2005) Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 46:205–217. doi:10.1016/j.neuron.2005.03.019

    Article  CAS  PubMed  Google Scholar 

  100. Sahin M, Greer PL, Lin MZ et al (2005) Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse. Neuron 46:191–204. doi:10.1016/j.neuron.2005.01.030

    Article  CAS  PubMed  Google Scholar 

  101. Hiramoto-Yamaki N, Takeuchi S, Ueda S et al (2010) Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. J Cell Biol 190:461–477. doi:10.1074/jbc.M608509200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Moeller ML, Shi Y, Reichardt LF, Ethell IM (2006) EphB receptors regulate dendritic spine morphogenesis through the recruitment/phosphorylation of focal adhesion kinase and RhoA activation. J Biol Chem 281:1587–1598. doi:10.1074/jbc.M511756200

    Article  CAS  PubMed  Google Scholar 

  103. Vindis C, Teli T, Cerretti DP et al (2004) EphB1-mediated cell migration requires the phosphorylation of paxillin at Tyr-31/Tyr-118. J Biol Chem 279:27965–27970. doi:10.1074/jbc.M401295200

    Article  CAS  PubMed  Google Scholar 

  104. Carter N, Nakamoto T, Hirai H, Hunter T (2002) EphrinA1-induced cytoskeletal re-organization requires FAK and p130(cas). Nat Cell Biol 4:565–573. doi:10.1038/ncb823

    CAS  PubMed  Google Scholar 

  105. Iwasato T, Katoh H, Nishimaru H et al (2007) Rac-GAP alpha-chimerin regulates motor-circuit formation as a key mediator of EphrinB3/EphA4 forward signaling. Cell 130:742–753. doi:10.1016/j.cell.2007.07.022

    Article  CAS  PubMed  Google Scholar 

  106. Bong Y-S, Lee H-S, Carim-Todd L et al (2007) ephrinB1 signals from the cell surface to the nucleus by recruitment of STAT3. Proc Natl Acad Sci USA 104:17305–17310. doi:10.1073/pnas.0702337104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  107. Becker E, Huynh-Do U, Holland S et al (2000) Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation. Mol Cell Biol 20:1537–1545

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  108. Miao H, Wei BR, Peehl DM et al (2001) Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat Cell Biol 3:527–530. doi:10.1038/35074604

    Article  CAS  PubMed  Google Scholar 

  109. Genander M, Halford MM, Xu N-J et al (2009) Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell 139:679–692. doi:10.1016/j.cell.2009.08.048

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Filas BA, Oltean A, Majidi S et al (2012) Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain. Phys Biol 9:066007. doi:10.1088/1478-3975/9/6/066007

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to members of Pujades lab for insightful discussions. JT was recipient of Beatriu de Pinos postdoctoral contract from AGAUR (Generalitat de Catalunya). This work was funded by BFU2012-31994 (Spanish Ministry of Economy and Competitiveness, MINECO) to CP.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cristina Pujades.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Terriente, J., Pujades, C. Cell segregation in the vertebrate hindbrain: a matter of boundaries. Cell. Mol. Life Sci. 72, 3721–3730 (2015). https://doi.org/10.1007/s00018-015-1953-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-015-1953-8

Keywords

Navigation