title: Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification.
abstract: 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.
authors.affiliation: UMR 643, INSERM, Nantes, 44000, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Angibaud
authors.forename: Stéphane J
authors.initials: SJ
authors.lastname: Baudouin
authors.forename: Antoine
authors.initials: A
authors.lastname: Louveau
authors.forename: Véronique
authors.initials: V
authors.lastname: Nerrière-Daguin
authors.forename: Virginie
authors.initials: V
authors.lastname: Bonnamain
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Csaba
authors.forename: Pascal
authors.initials: P
authors.lastname: Dournaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Naveilhan
authors.forename: Nelly
authors.initials: N
authors.lastname: Noraz
authors.forename: Véronique
authors.initials: V
authors.lastname: Pellier-Monnin
authors.forename: Hélène
authors.initials: H
authors.lastname: Boudin
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured / Q000201:enzymology; D004790:Enzyme Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000201:enzymology* / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D009830:Olfactory Bulb / Q000196:embryology / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D014162:Transfection
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins