Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants

Autor: Maurizio Cavallaro, Elisa Latorre, Silvia DeBiasi, Antonella Ronchi, Francesca Gullo, Silvia Brunelli, Jessica Mariani, Rebecca Favaro, Menella Valotta, Silvia K. Nicolis, Enzo Wanke, Laura Spinardi, Roberta Caccia, Cesare Lancini, Sergio Ottolenghi
Přispěvatelé: Cavallaro, M, Mariani, J, Lancini, C, Latorre, E, Caccia, R, Gullo, F, Valotta, M, Debiasi, S, Spinardi, L, Ronchi, A, Wanke, E, Brunelli, S, Favaro, R, Ottolenghi, S, Nicolis, S
Rok vydání: 2008
Předmět:
Transcription Factor
Calcium-Binding Protein
Vitamin D-Dependent
Cellular differentiation
Fluorescent Antibody Technique
Mice
Tubulin
Cells
Cultured
gamma-Aminobutyric Acid
Neurons
Stem Cells
Neurogenesis
Brain
Cell Differentiation
Olfactory Bulb
Chromatin
Neural stem cell
Cell biology
DNA-Binding Proteins
Neuroepithelial cell
Calbindin 2
Stem cell
Neuroglia
Adult stem cell
DNA-Binding Protein
SOXB1 Transcription Factor
Biology
Lentiviru
S100 Calcium Binding Protein G
SOX2
Stem Cell
HMGB Proteins
Neurosphere
Glial Fibrillary Acidic Protein
Animals
Molecular Biology
Animal
HMGB Protein
SOXB1 Transcription Factors
Lentivirus
DNA
Somatosensory Cortex
Neuron
Mice
Mutant Strains
Animals
Newborn
nervous system
Biological Marker
Mutation
Immunology
Mice
Mutant Strain
Biomarkers
Transcription Factors
Developmental Biology
Zdroj: Development. 135:541-557
ISSN: 1477-9129
0950-1991
Popis: The transcription factor Sox2 is active in neural stem cells, and Sox2`knockdown' mice show defects in neural stem/progenitor cells in the hippocampus and eye, and possibly some neurons. In humans, heterozygous Sox2 deficiency is associated with eye abnormalities, hippocampal malformation and epilepsy. To better understand the role of Sox2, we performed in vitro differentiation studies on neural stem cells cultured from embryonic and adult brains of `knockdown' mutants. Sox2 expression is high in undifferentiated cells, and declines with differentiation, but remains visible in at least some of the mature neurons. In mutant cells, neuronal, but not astroglial,differentiation was profoundly affected. β-Tubulin-positive cells were abundant, but most failed to progress to more mature neurons, and showed morphological abnormalities. Overexpression of Sox2 in neural cells at early,but not late, stages of differentiation, rescued the neuronal maturation defect. In addition, it suppressed GFAP expression in glial cells. Our results show an in vitro requirement for Sox2 in early differentiating neuronal lineage cells, for maturation and for suppression of alternative lineage markers. Finally, we examined newly generated neurons from Sox2 `knockdown'newborn and adult mice. GABAergic neurons were greatly diminished in number in newborn mouse cortex and in the adult olfactory bulb, and some showed abnormal morphology and migration properties. GABA deficiency represents a plausible explanation for the epilepsy observed in some of the knockdown mice, as well as in SOX2-deficient individuals.
Databáze: OpenAIRE
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