Regulation of neural migration by the CREB/CREM transcription factors and altered Dab1 levels in CREB/CREM mutants.

The family of CREB transcription factors is involved in a variety of biological processes including the development and plasticity of the nervous system. To gain further insight into the roles of CREB family members in the development of the embryonic brain, we examined the migratory phenotype of CREB1(Nescre)CREM(-/-) mutants. We found that the lack of CREB/CREM genes is accompanied by anatomical defects in specific layers of the olfactory bulb, hippocampus and cerebral cortex. These changes are associated with decreased Dab1 expression in CREB1(Nescre)CREM(-/-) mutants. Our results indicate that the lack of CREB/CREM genes, specifically in neural and glial progenitors, leads to migration abnormalities during brain development, suggesting that unidentified age-dependent factors modulate the role of CREB/CREM genes in neural development.