title: ALK5-dependent TGF-β signaling is a major determinant of late-stage adult neurogenesis.
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.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Yung
authors.affiliation: Present address: The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, USA (S.A.V.), Department of Bioengineering, University of California San Diego, La Jolla, California, USA, and Department of Medicine, University of California San Diego, La Jolla, California, USA (P.A.J.).
authors.forename: Saul A
authors.initials: SA
authors.lastname: Villeda
authors.affiliation: Present address: The Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, USA (S.A.V.), Department of Bioengineering, University of California San Diego, La Jolla, California, USA, and Department of Medicine, University of California San Diego, La Jolla, California, USA (P.A.J.).
authors.forename: Philipp A
authors.identifier: 0000000236240802
authors.initials: PA
authors.lastname: Jaeger
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Oluwatobi
authors.initials: O
authors.lastname: Olayiwola
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Fainberg
authors.affiliation: 1] Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA. [2] Center for Tissue Regeneration, Repair and Rehabilitation, VA Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D003213:Conditioning, Psychological; D018891:Dentate Gyrus / Q000502:physiology; D000229:Dependovirus; D004318:Doxycycline / Q000494:pharmacology; D005239:Fear / Q000523:psychology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D006624:Hippocampus / Q000254:growth & development* / Q000502:physiology; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013238:Stereotaxic Techniques; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse; D004318:Doxycycline