1. ALK5-dependent TGF-β signaling is a major determinant of late-stage adult neurogenesis.
- Author
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He Y, Zhang H, Yung A, Villeda SA, Jaeger PA, Olayiwola O, Fainberg N, and Wyss-Coray T
- Subjects
- Animals, Animals, Newborn, Blotting, Western, Conditioning, Psychological, Dentate Gyrus physiology, Dependovirus, Doxycycline pharmacology, Fear psychology, Female, Gene Expression physiology, Genetic Vectors, Hippocampus physiology, Immunohistochemistry, Luciferases genetics, Male, Memory physiology, Mice, Mice, Inbred C57BL, Microarray Analysis, Microscopy, Confocal, Neurons physiology, Receptor, Transforming Growth Factor-beta Type I, Stereotaxic Techniques, Hippocampus growth & development, Neurogenesis physiology, Protein Serine-Threonine Kinases physiology, Receptors, Transforming Growth Factor beta physiology, Signal Transduction physiology, Transforming Growth Factor beta physiology
- Abstract
The transforming growth factor-β (TGF-β) signaling pathway serves critical functions in CNS development, but, apart from its proposed neuroprotective actions, its physiological role in the adult brain is unclear. We observed a prominent activation of TGF-β signaling in the adult dentate gyrus and expression of downstream Smad proteins in this neurogenic zone. Consistent with a function of TGF-β signaling in adult neurogenesis, genetic deletion of the TGF-β receptor ALK5 reduced the number, migration and dendritic arborization of newborn neurons. Conversely, constitutive activation of neuronal ALK5 in forebrain caused a marked increase in these aspects of neurogenesis and was associated with higher expression of c-Fos in newborn neurons and with stronger memory function. Our findings describe an unexpected role for ALK5-dependent TGF-β signaling as a regulator of the late stages of adult hippocampal neurogenesis, which may have implications for changes in neurogenesis during aging and disease.
- Published
- 2014
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