1. E-Cadherin regulates neural stem cell self-renewal.
- Author
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Karpowicz P, Willaime-Morawek S, Balenci L, DeVeale B, Inoue T, and van der Kooy D
- Subjects
- Adult Stem Cells cytology, Adult Stem Cells metabolism, Animals, Cadherins genetics, Cell Proliferation, Cells, Cultured, Crosses, Genetic, Embryonic Stem Cells cytology, Embryonic Stem Cells metabolism, Mice, Mice, Transgenic, Mutation, Neurons metabolism, Prosencephalon cytology, Spheroids, Cellular cytology, Spheroids, Cellular metabolism, Stem Cells metabolism, Cadherins physiology, Neurons cytology, Prosencephalon metabolism, Stem Cells cytology
- Abstract
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.
- Published
- 2009
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