title: CREB signalling regulates early survival, neuronal gene expression and morphological development in adult subventricular zone neurogenesis.
abstract: Neural stem cells in the subventricular zone (SVZ) of the lateral ventricles give rise to new interneurons of the olfactory bulb (OB) throughout life. SVZ/OB neurogenesis is influenced by olfactory network activity, which modulates the survival of new neurons during their integration into the OB network. Previous work suggested that such activity-dependent survival is regulated via the CREB signalling pathway. Curiously, CREB signalling is already active during the early developmental stages of adult SVZ/OB neurogenesis. To investigate the role of cell autonomous CREB signalling during early stages of adult SVZ/OB neurogenesis, we ablated CREB-pathway activity in the SVZ/OB neurogenic lineage using a retroviral strategy. Surprisingly, loss of CREB signalling resulted in increased cell death and loss of expression of the neurogenic transcription factor Pax 6, and of a subset of neuronal proteins in migrating neurons of the RMS. Moreover, post-migratory neurons in the OB displayed impaired dendritic development. These results demonstrate an essential role for CREB signalling in maturation of newborn neurons in the OB and uncover a novel role for CREB signalling in the survival and maintenance of neuronal gene expression during the early stages of SVZ/OB neurogenesis.
authors.affiliation: Research Group Adult Neurogenesis and Neural Stem Cells, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Herold
authors.forename: R
authors.initials: R
authors.lastname: Jagasia
authors.forename: K
authors.initials: K
authors.lastname: Merz
authors.forename: K
authors.initials: K
authors.lastname: Wassmer
authors.forename: D C
authors.initials: DC
authors.lastname: Lie
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D020547:Lateral Ventricles / Q000033:anatomy & histology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins