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Asymmetric localization of Notch2 on the microvillous surface in choroid plexus epithelial cells

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Abstract

Notch family molecules are transmembrane receptors that play various roles in contact-dependent cell–cell interactions in a wide range of organs. In the brain, Notch2, but not the other members of Notch, is expressed in the choroid plexus at an exceptionally high level. We immunohistochemically examined the cellular and subcellular localization of Notch2 protein in the choroid plexus using confocal and electron microscopy. Unexpectedly, Notch2 was asymmetrically localized on the microvillous surface of epithelial cells in the choroid plexus of both postnatal and adult rats. This localization pattern of Notch2 suggests its novel and unknown role independent of contact with adjacent cells in the choroid plexus. In organotypic cultures of the choroid plexus, the addition of anti-Notch2 antibody resulted in deformation of microvilli in epithelial cells, which suggests a role of Notch2 in the maintenance of the microvillous structure in choroid plexus epithelial cells.

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References

  • Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776

    Article  PubMed  CAS  Google Scholar 

  • Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7:678–689

    Article  PubMed  CAS  Google Scholar 

  • Cheuk W, Chan JKC (2004) Subcellular localization of immunohistochemical signals. Int J Surg Pathol 12:185–206

    Article  PubMed  CAS  Google Scholar 

  • Chodobski A, Szmydynger-Chodobska J (2001) Choroid plexus: target for polypeptides and site of their synthesis. Microsc Res Tech 52:65–82

    Article  PubMed  CAS  Google Scholar 

  • Del Amo FF, Smith DE, Swiatek PJ, Gendron-Maguire M, Greenspan PJ, McMahon AP, Gridley T (1992) Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development. Development 115:737–744

    PubMed  Google Scholar 

  • Emerich DF, Skinner SJM, Borlongan CV, Vasconcellos AV, Thanos CG (2005) The choroid plexus in the rise, fall and repair of the brain. Bioessays 27:262–274

    Article  PubMed  CAS  Google Scholar 

  • Farrell CL, Yang J, Pardridge WM (1992) GLUT-1 glucose transporter is present within apical and basolateral membranes of brain epithelial interfaces and in microvascular endothelia with and without tight junctions. J Histochem Cytochem 40:193–199

    PubMed  CAS  Google Scholar 

  • Fehon RG, Johansen K, Rebay I, Artavanis-Tsakonas S (1991) Complex cellular and subcellular regulation of Notch expression during embryonic and imaginal development of Drosophila: implications for Notch function. J Cell Biol 113:657–669

    Article  PubMed  CAS  Google Scholar 

  • Figarella-Branger D, Lepidi H, Poncet C, Gambarelli D, Bianco N, Rougon G, Pellissier JF (1995) Differential expression of cell adhesion molecules (CAM), neural CAM and epithelial cadherin in ependymomas and choroid plexus tumors. Acta Neuropathol (Berl) 89:248–257

    CAS  Google Scholar 

  • Freshney RI (1987) Three-dimensional culture systems. In: Culture of animal cells: a manual of basic technique, 2nd edn. Alan R. Liss Inc., New York, pp 297–307

    Google Scholar 

  • Gaiano N, Fishell G (2002) The role of Notch in promoting glial and neural stem cell fates. Annu Rev Neurosci 25:471–490

    Article  PubMed  CAS  Google Scholar 

  • Harik SI, Kalaria RN, Andersson L, Lundahl P, Perry G (1990) Immunocytochemical localization of the erythroid glucose transporter: abundance in tissues with barrier functions. J Neurosci 10:3862–3872

    PubMed  CAS  Google Scholar 

  • Higuchi M, Kiyama H, Hayakawa T, Hamada Y, Tsujimoto Y (1995) Differential expression of Notch1 and Notch2 in developing and adult mouse brain. Mol Brain Res 29:263–272

    Article  PubMed  CAS  Google Scholar 

  • Irvin DK, Nakano I, Paucar A, Kornblum HI (2004) Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 expression during late embryonic and postnatal brain development suggest multiple functional roles in progenitors and differentiated cells. J Neurosci Res 75:330–343

    Article  PubMed  CAS  Google Scholar 

  • Irvin DK, Zurcher SD, Nguyen T, Weinmaster G, Kornblum HI (2001) Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. J Comp Neurol 436:167–181

    Article  PubMed  CAS  Google Scholar 

  • Knuesel I, Bornhauser BC, Zuellig RA, Heller F, Schaub MC, Fritschy J-M (2000) Differential expression of utrophin and dystrophin in CNS neurons: an in situ hybridization and immunohistochemical study. J Comp Neurol 422:594–611

    Article  PubMed  CAS  Google Scholar 

  • Lai EC (2004) Notch signaling: control of cell communication and cell fate. Development 131:965–973

    Article  PubMed  CAS  Google Scholar 

  • Lardelli M, Dahlstrand J, Lendahl U (1994) The novel Notch homologue mouse Notch 3 lacks specific epidermal growth factor-repeats and is expressed in proliferating neuroepithelium. Mech Dev 46:123–136

    Article  PubMed  CAS  Google Scholar 

  • Lindsell CE, Boulter J, diSibio G, Gossler A, Weinmaster G (1996) Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development. Mol Cell Neurosci 8:14–27

    Article  PubMed  CAS  Google Scholar 

  • Lippoldt A, Jansson A, Kniesel U, Andbjer B, Andersson A, Wolburg H, Fuxe K, Haller H (2000) Phorbol ester induced changes in tight and adherens junctions in the choroid plexus epithelium and in the ependyma. Brain Res 854:194–206

    Article  Google Scholar 

  • Louvi A, Artavanis-Tsakonas S (2006) Notch signalling in vertebrate neural development. Nat Rev Neurosci 7:93–102

    Article  PubMed  CAS  Google Scholar 

  • Masuzawa T, Ohta T, Kawamura M, Nakahara N, Sato F (1984) Immunohistochemical localization of Na+,K +-ATPase in the choroid plexus. Brain Res 302:357–362

    Article  PubMed  CAS  Google Scholar 

  • Nagata Y, Kusuhara H, Endou H, Sugiyama Y (2002) Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol 61:982–988

    Article  PubMed  CAS  Google Scholar 

  • Nualart F, Godoy A, Reinicke K (1999) Expression of the hexose transporters GLUT1 and GLUT2 during the early development of the human brain. Brain Res 824:97–104

    Article  PubMed  CAS  Google Scholar 

  • Rao VV, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC, Piwnica-Worms D (1999) Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc Natl Acad Sci 96:3900–3905

    Article  PubMed  CAS  Google Scholar 

  • Reaume AG, Conlon RA, Zirngibl R, Yamaguchi TP, Rossant J (1992) Expression analysis of a Notch homologue in the mouse embryo. Dev Biol 154:377–387

    Article  PubMed  CAS  Google Scholar 

  • Redzic ZB, Segal MB (2004) The structure of the choroid plexus and the physiology of the choroid plexus epithelium. Adv Drug Deliv Rev 56:1695–1716

    Article  PubMed  CAS  Google Scholar 

  • Shaye DD, Greenwald I (2002) Endocytosis-mediated downregulation of LIN12/Notch upon Ras activation in Caenorhabditis elegans. Nature 420:686–690

    Article  PubMed  CAS  Google Scholar 

  • Shen H, Smith DE, Keep RF, Brosius FC III (2004) Immunolocalization of the proton-coupled oligopeptide transporter PEPT2 in developing rat brain. Mol Pharm 1:248–256

    Article  PubMed  CAS  Google Scholar 

  • Siegel GJ, Holm C, Schreiber JH, Desmond T, Ernst SA (1984) Purification of mouse brain (Na+ + K +)-ATPase catalytic unit, characterization of antiserum, and immunocytochemical localization in cerebellum, choroid plexus, and kidney. J Histochem Cytochem 32:1309–1318

    PubMed  CAS  Google Scholar 

  • Soontornmalai A, Vlaming MLH, Fritschy JM (2006) Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood–brain barrier. Neuroscience 138:159–169

    Article  PubMed  CAS  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (2000) Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol 59:561–574

    PubMed  CAS  Google Scholar 

  • Tanaka M, Kadokawa Y, Hamada Y, Marunouchi T (1999) Notch2 expression negatively correlates with glial differentiation in the postnatal mouse brain. J Neurobiol 41:524–539

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Tomita A, Yoshida S, Yano M, Shimizu H (1994) Observation of the highly organized development of granule cells in rat cerebellar organotypic cultures. Brain Res 641:319–327

    Article  PubMed  CAS  Google Scholar 

  • Weinmaster G, Roberts VJ, Lemke G (1991) A homolog of Drosophila Notch expressed during mammalian development. Development 113:119–205

    Google Scholar 

  • Weinmaster G, Roberts VJ, Lemke G (1992) Notch2: a second mammalian Notch gene. Development 116:931–941

    PubMed  CAS  Google Scholar 

  • Wilson A, Radtke F (2006) Multiple functions of Notch signaling in self-renewing organs and cancer. FEBS Lett 580:2860–2868

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a grant-in-aid for scientific research from Fujita Health University.

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  1. Masahiko Tanaka

    Present address: Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, 467-8603, Japan

Authors and Affiliations

  1. Division of Cell Biology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan

    Masahiko Tanaka & Tohru Marunouchi

  2. Joint Research Laboratory, Cooperation Use Study Room Facilities, Fujita Health University, Toyoake, Aichi, 470-1192, Japan

    Masahiro Kokubo

Authors
  1. Masahiko Tanaka
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Correspondence to Masahiko Tanaka.

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Tanaka, M., Kokubo, M. & Marunouchi, T. Asymmetric localization of Notch2 on the microvillous surface in choroid plexus epithelial cells. Histochem Cell Biol 127, 449–456 (2007). https://doi.org/10.1007/s00418-006-0260-8

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