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E-Cadherin regulates neural stem cell self-renewal

By P. Karpowicz, S. Willaime-Morawek, L. Balenci, B. DeVeale, T. Inoue and D. van der Kooy


E-Cadherin, a cell adhesion protein, has been shown to take part in the compartmentalization, proliferation, survival, and differentiation of cells. E-Cadherin is expressed in the adult and embryonic forebrain germinal zones in vivo, and in clonal colonies of cells derived from these regions and grown in vitro. Mice carrying E-Cadherin floxed genes crossed to mice expressing Cre under the Nestin promoter demonstrate defects in the self-renewal of neural stem cells both in vivo and in vitro. The functional role of E-Cadherin is further demonstrated using adhesion-blocking antibodies in vitro, which specifically target cadherin extracellular adhesive domains. Adult neural stem cell colonies decrease in the presence of E-Cadherin antibodies in a dosage-dependent manner, in contrast to P-Cadherin antibody. On overexpression of normal E-Cadherin and a mutated E-Cadherin, containing no intracellular binding domain, an increased number of clonal adult neural stem cell colonies are observed. These data suggest it is specifically E-Cadherin adhesion that is responsible for these self-renewal effects. These data show the importance of E-Cadherin in the neural stem cell niche and suggest E-Cadherin regulates the number of these cells

Topics: RC0321, QH426
Year: 2009
OAI identifier: oai:eprints.soton.ac.uk:66445
Provided by: e-Prints Soton

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  1. (1992). A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.
  2. (2001). A new “spin” on neural stem cells?
  3. (1996). A role for cadherins in tissue formation.
  4. (2006). alphaE-catenin controls cerebral cortical size by regulating the hedgehog signaling pathway.
  5. (2001). Aunifiedhypothesis on the lineage of neural stem cells.
  6. (2003). Cadherin-mediatedcell interaction regulates germ cell determination in mice.
  7. (2000). Cadherins in the central nervous system. Prog Neurobiol 61:611–648.
  8. (2004). Conditional targeting of E-cadherin in skin: insights into hyperproliferative and degenerative responses.
  9. (1999). Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon.
  10. (2006). E-cadherin engagement stimulates proliferation via Rac1.
  11. (2007). E-cadherin homophilic ligation inhibits cell growth and epidermal growth factor receptor signaling independently of other cell interactions.
  12. (2002). E-cadherin is a survival factor for the lactating mouse mammary gland.
  13. (2001). E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesionindependent manner.
  14. (1994). E-cadherinnullmutant embryos fail to form a trophectoderm epithelium.
  15. (1994). Experimentalspecificationofcellsorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression.
  16. (1995). Fetal brain subdivisions defined by Rand E-cadherin expressions: evidence for the role of cadherin activity in region-specific, cell-cell adhesion.
  17. (2004). For the long run: maintaining germinal niches in the adult brain.
  18. (2004). Gap junctional communication is required to maintain mouse cortical neural progenitor cells in a proliferative state.
  19. (2002). Germline stem cells anchored by adherens junctions in the Drosophila ovary niches.
  20. (2007). IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro.
  21. (1998). In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain.
  22. (2006). Inactivation of aPKClambda results inthelossofadherensjunctionsinneuroepithelialcellswithoutaffecting neurogenesis in mouse neocortex.
  23. Knoblich JA (2004) Dare to be different: asymmetric cell divisioninDrosophila,C.elegansandvertebrates.CurrBiol14:R674–R685.
  24. (1992). Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis. Development 116:1011–1019.
  25. (1994). Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells.
  26. (2007). Notch signaling controls germline stem cell niche formation in the Drosophila ovary.
  27. (2006). Notch, epidermal growth factor receptor, and beta1-integrin pathways are coordinated in neural stem cells.
  28. (2002). Notchpathwaymolecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16:846–858.
  29. (2006). Notchsignallinginvertebrateneural development.
  30. (2007). NumbandNumblarerequired for maintenance of cadherin-based adhesion and polarity of neural progenitors.
  31. (2003). Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome.
  32. (2005). p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev 19:756–767.
  33. (2004). Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo.
  34. Sestan N,Garcia-VerdugoJ,Alvarez-BuyllaA,JanLY,JanYN (2006) Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche.
  35. (2004). Spradling A
  36. (2006). Stem cells signal to the niche through the Notch pathway in the Drosophila ovary.
  37. (2001). Stem cells, cancer, and cancer stem cells.
  38. (2005). Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro.
  39. (2003). The ablation of glial fibrillary acidic protein-positive cells from the adult centralnervoussystemresultsinthelossofforebrainneuralstemcellsbutnot retinal stem cells.
  40. (2003). The predominant neural stemcellisolatedfrompostnatalandadultforebrainbutnotearlyembryonic forebrain expresses GFAP. J Neurosci 23:2824–2832. JinZ,KirillyD,WengC,KawaseE,SongX,SmithS,SchwartzJ,XieT
  41. (2000). The role of cadherins during primordial germ cell migration and early gonad formation in the mouse. Mech Dev 91:143–152.
  42. (1999). The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 24:73–76.
  43. (1997). The tao of stem cells in the germline. Annu Rev Genet 31:455–491.
  44. (2005). Thedifferentialadhesionhypothesis:adirect evaluation.
  45. (2004). Thestemcellniche:theme and variations.
  46. (1999). TroncheF,KellendonkC,KretzO,GassP,AnlagK,OrbanPC,BockR,Klein R,Schu ¨tzG

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