CoChat
Sign Up
Cited by 793

Wnt/β-catenin signaling controls development of the blood–brain barrier

Liebner, Stefan, Corada, Monica, Bangsow, Thorsten, Babbage, Jane, Taddei, Andrea, Czupalla, Cathrin J., Reis, Marco, Felici, Angelina +7 more·2008·The Journal of Cell Biology
DOI 10.1083/jcb.200806024PMC PMC2575783
Open this paper in CoChat — free account

Abstract

The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1083/jcb.200806024

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • During embryogenesis, neural progenitors secrete Wnt ligands, which activate canonical Wnt signaling in ECs and contribute to maturation of brain vasculature.

    “During embryogenesis, neural progenitors secrete Wnt ligands, which activate canonical Wnt signaling in ECs and contribute to the maturation of brain vasculature6,7,8.”

    From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [8]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 30

  1. Brault, V., R. Moore, S. Kutsch, M. Ishibashi, D.H. Rowitch, A.P. McMahon, L. Sommer, O. Boussadia, and R. Kemler. 2001. Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development. 128: 1253–1264. 11262227
  2. Calabria, A.R., C. Weidenfeller, A.R. Jones, H.E. de Vries, and E.V. Shusta. 2006. Puromycin-purified rat brain microvascular endothelial cell cultures exhibit improved barrier properties in response to glucocorticoid induction. J. Neurochem. 97: 922–933. 16573646
  3. Carson-Walter, E.B., J. Hampton, E. Shue, D.M. Geynisman, P.K. Pillai, R. Sathanoori, S.L. Madden, R.L. Hamilton, and K.A. Walter. 2005. Plasmalemmal vesicle associated protein-1 is a novel marker implicated in brain tumor angiogenesis. Clin. Cancer Res. 11: 7643–7650. 16278383
  4. Cattelino, A., S. Liebner, R. Gallini, A. Zanetti, G. Balconi, A. Corsi, P. Bianco, H. Wolburg, R. Moore, B. Oreda, et al. 2003. The conditional inactivation of the β-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility. J. Cell Biol. 162: 1111–1122. 12975353 PMC2172846
  5. Chen, W., D. ten Berge, J. Brown, S. Ahn, L.A. Hu, W.E. Miller, M.G. Caron, L.S. Barak, R. Nusse, and R.J. Lefkowitz. 2003. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science. 301: 1391–1394. 12958364
  6. Claxton, S., V. Kostourou, S. Jadeja, P. Chambon, K. Hodivala-Dilke, and M. Fruttiger. 2008. Efficient, inducible Cre-recombinase activation in vascular endothelium. Genesis. 46: 74–80. 18257043
  7. Dull, T., R. Zufferey, M. Kelly, R.J. Mandel, M. Nguyen, D. Trono, and L. Naldini. 1998. A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72: 8463–8471. 9765382 PMC110254
  8. Engelhardt, B. 2003. Development of the blood-brain barrier. Cell Tissue Res. 314: 119–129. 12955493
  9. Engelhardt, B. 2006. Molecular mechanisms involved in T cell migration across the blood-brain barrier. J. Neural Transm. 113: 477–485. 16550326
  10. Furuse, M., and S. Tsukita. 2006. Claudins in occluding junctions of humans and flies. Trends Cell Biol. 16: 181–188. 16537104
  11. Gerhardt, H., M. Golding, M. Fruttiger, C. Ruhrberg, A. Lundkvist, A. Abramsson, M. Jeltsch, C. Mitchell, K. Alitalo, D. Shima, and C. Betsholtz. 2003. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161: 1163–1177. 12810700 PMC2172999
  12. Hallmann, R., D.N. Mayer, E.L. Berg, R. Broermann, and E.C. Butcher. 1995. Novel mouse endothelial cell surface marker is suppressed during differentiation of the blood brain barrier. Dev. Dyn. 202: 325–332. 7626790
  13. Hamer, P.W., J.M. McGeachie, M.J. Davies, and M.D. Grounds. 2002. Evans Blue dye as an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability. J. Anat. 200: 69–79. 11837252 PMC1570883
  14. Harada, N., Y. Tamai, T. Ishikawa, B. Sauer, K. Takaku, M. Oshima, and M.M. Taketo. 1999. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J. 18: 5931–5942. 10545105 PMC1171659
  15. Kniesel, U., W. Risau, and H. Wolburg. 1996. Development of blood-brain barrier tight junctions in the rat cortex. Brain Res. Dev. Brain Res. 96: 229–240. 8922685
  16. Lampugnani, M.G., A. Zanetti, F. Breviario, G. Balconi, F. Orsenigo, M. Corada, R. Spagnuolo, M. Betson, V. Braga, and E. Dejana. 2002. VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. Mol. Biol. Cell. 13: 1175–1189. 11950930 PMC102260
  17. Liebner, S., A. Fischmann, G. Rascher, F. Duffner, E.H. Grote, H. Kalbacher, and H. Wolburg. 2000a. Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 100: 323–331. 10965803
  18. Liebner, S., U. Kniesel, H. Kalbacher, and H. Wolburg. 2000b. Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur. J. Cell Biol. 79: 707–717. 11089919
  19. Liebner, S., A. Cattelino, R. Gallini, N. Rudini, M. Iurlaro, S. Piccolo, and E. Dejana. 2004. β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J. Cell Biol. 166: 359–367. 15289495 PMC2172268
  20. Lim, J.C., K.D. Kania, H. Wijesuriya, S. Chawla, J.K. Sethi, L. Pulaski, I.A. Romero, P.O. Couraud, B.B. Weksler, S.B. Hladky, and M.A. Barrand. 2008. Activation of beta-catenin signalling by GSK-3 inhibition increases p-glycoprotein expression in brain endothelial cells. J. Neurochem. 106: 1855–1865. 18624906 PMC4303914
  21. Maretto, S., M. Cordenonsi, S. Dupont, P. Braghetta, V. Broccoli, A.B. Hassan, D. Volpin, G.M. Bressan, and S. Piccolo. 2003. Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc. Natl. Acad. Sci. USA. 100: 3299–3304. 12626757 PMC152286
  22. Moon, R.T. 2005. Wnt/beta-catenin pathway. Sci. STKE. doi: 10.1126/stke.2712005cm1. 15713948 · DOI
  23. Quasnichka, H., S.C. Slater, C.A. Beeching, M. Boehm, G.B. Sala-Newby, and S.J. George. 2006. Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21 expression. Circ. Res. 99: 1329–1337. 17122440
  24. Sparks, D.L., Y.M. Kuo, A. Roher, T. Martin, and R.J. Lukas. 2000. Alterations of Alzheimer's disease in the cholesterol-fed rabbit, including vascular inflammation. Preliminary observations. Ann. NY Acad. Sci. 903: 335–344. 10818523
  25. Srinivas, S., T. Watanabe, C.S. Lin, C.M. William, Y. Tanabe, T.M. Jessell, and F. Costantini. 2001. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol. 1: 4. 11299042 PMC31338
  26. Taddei, A., C. Giampietro, A. Conti, F. Orsenigo, F. Breviario, V. Pirazzoli, M. Potente, C. Daly, S. Dimmeler, and E. Dejana. 2008. Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat. Cell Biol. 10: 923–934. 18604199
  27. Vecchi, A., C. Garlanda, M.G. Lampugnani, M. Resnati, C. Matteucci, A. Stoppacciaro, H. Schnurch, W. Risau, L. Ruco, A. Mantovani, et al. 1994. Monoclonal antibodies specific for endothelial cells of mouse blood vessels. Their application in the identification of adult and embryonic endothelium. Eur. J. Cell Biol. 63: 247–254. 8082649
  28. Vleminckx, K., R. Kemler, and A. Hecht. 1999. The C-terminal transactivation domain of beta-catenin is necessary and sufficient for signaling by the LEF-1/beta-catenin complex in Xenopus laevis. Mech. Dev. 81: 65–74. 10330485
  29. Wadia, J.S., R.V. Stan, and S.F. Dowdy. 2004. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat. Med. 10: 310–315. 14770178
  30. Wolburg, H., K. Wolburg-Buchholz, J. Kraus, G. Rascher-Eggstein, S. Liebner, S. Hamm, F. Duffner, E.H. Grote, W. Risau, and B. Engelhardt. 2003. Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol. 105: 586–592. 12734665

Cited by

Sorted by citations

Authors
Liebner, S., Corada, M., Bangsow, T., Babbage, J., Taddei, A., Czupalla, C. J., Reis, M., Felici, A., Wolburg, H., Fruttiger, M., Taketo, M. M., von Melchner, H., Plate, K. H., Gerhardt, H., & Dejana, E.
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2008-10-27
Volume
183
Issue
3
Pages
409-417
ISSN
  • 1540-8140
  • 0021-9525
DOI
10.1083/jcb.200806024
PMC
PMC2575783
Cited by
793
References
2
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review