Related Experiment Video
Updated: Aug 11, 2026
Whole-mount Imaging of Mouse Embryo Sensory Axon Projections
Published on: December 9, 2014
Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB
Bonnie E Lonze1, Antonella Riccio, Sonia Cohen
1Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abstract:
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.
Insights
The transcription factor CREB (cAMP response element-binding protein) is crucial for sensory neuron survival and axon growth. Its absence leads to degeneration in peripheral neurons but not the central nervous system.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- CREB (cAMP response element-binding protein) is a transcription factor involved in gene expression.
- Neurotrophins regulate neuronal survival and growth.
- The role of CREB in neurotrophin-dependent processes in peripheral neurons is not fully understood.
Purpose of the Study:
- To investigate the role of CREB phosphorylation at Ser-133 in neurotrophin-dependent gene expression.
- To determine the in vivo function of CREB in neuronal survival and axonal growth.
Main Methods:
- Analysis of CREB phosphorylation in vivo.
- Generation and study of mice with a null mutation in the Creb gene.
- Culturing of neurons from CREB null mice to assess survival and axon extension.
Main Results:
- CREB is phosphorylated at Ser-133 in a neurotrophin-dependent manner in vivo.
- CREB null mice exhibit sensory neuron degeneration and impaired axonal projections.
- Peripheral neurons from CREB null mice show compromised survival and axon extension in culture.
- Excess apoptosis is not observed in the central nervous system of CREB null mice.
Conclusions:
- CREB-mediated gene expression is essential for the survival and growth of peripheral neurons during their neurotrophin-dependent period.
- CREB plays a critical role in maintaining the integrity and function of sensory and sympathetic neurons.
- The function of CREB in neuronal survival and growth appears to be specific to the peripheral nervous system.
