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Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification

Angibaud, Julie, Baudouin, Stephane J., Louveau, Antoine, Nerrière-Daguin, Véronique, Bonnamain, Virginie, Csaba, Zsolt, Dournaud, Pascal, Naveilhan, Philippe, Noraz, Nelly, Pellier-Monnin, Véronique and Boudin, Hélène 2011. Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification. Journal of Molecular Neuroscience 46 (2) , pp. 431-441. 10.1007/s12031-011-9607-2

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Immune signaling and neuroinflammatory mediators have recently emerged as influential variables that regulate neural precursor/stem cell (NPC) behavior and function. In this study, we investigated whether the signaling adaptor protein CD3ζ, a transmembrane protein involved in T cell differentiation and function and recently shown to regulate neuronal development in the central nervous system (CNS), may have a role in NPC differentiation. We analyzed the expression profile of CD3ζ in embryonic rat brain during neurogenic periods and in neurosphere-derived neural cells, and we investigated the action of CD3ζ on cell differentiation. We found that CD3ζ expression coincided with neuronal commitment, but its forced expression in NPCs prevented the production of neurons and oligodendrocytes, but not astroglial cells. This blockade of neuronal differentiation was operated through an ITAM-independent mechanism, but required the Asp36 of the CD3ζ transmembrane domain involved in membrane receptor interaction. Together, our findings show that ectopic CD3ζ expression in NPCs impaired their normal cell-fate specification and suggest that variations of CD3ζ expression in the developing CNS might result in neurodevelopmental anomalies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Neuronal differentiation; Neurosphere; Neurogenesis; Neural stem cell; Neuroimmunology; Neuroinflammation
Publisher: Springer
ISSN: 0895-8696
Last Modified: 04 Jun 2017 06:11

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