Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB.
CRE-binding protein (CREB) belongs to a family of transcription factors that mediates stimulus-dependent gene expression in neuronal and non-neuronal cells. Here we show that CREB is phosphorylated on its transcriptional regulatory site, Ser-133, in vivo in a neurotrophin-dependent manner. In mice harboring a null mutation in the Creb gene, sensory neurons exhibit excess apoptosis and degeneration, and display impaired axonal growth and projections. Interestingly, excess apoptosis is not observed in the central nervous system. CREB is required within sensory and sympathetic neurons for survival and axon extension since both of these neurotrophin-dependent processes are compromised in cultured neurons from CREB null mice. Thus, during their period of neurotrophin dependency, peripheral neurons require CREB-mediated gene expression for both survival and growth in vivo.
Lonze
Bonnie E
BE
Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Riccio
Antonella
A
Cohen
Sonia
S
Ginty
David D
DD
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein