CREB signalling regulates early survival, neuronal gene expression and morphological development in adult subventricular zone neurogenesis

Mol Cell Neurosci. 2011 Jan;46(1):79-88. doi: 10.1016/j.mcn.2010.08.008. Epub 2010 Aug 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / physiology
  • Cell Differentiation / physiology
  • Cell Lineage
  • Cell Survival*
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Lateral Ventricles / anatomy & histology*
  • Lateral Ventricles / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology
  • Neural Stem Cells / physiology*
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / physiology
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction / physiology*


  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins