Search

The nervous system contains a multitude of cell types which are specified during development by cascades of transcription factors acting combinatorially. Some of these transcription factors are only active during development, whereas others continue to function in the mature nervous system to maintain appropriate gene-expression patterns in differentiated cells. Underpinning the function of the nervous system is its plasticity in response to external stimuli, and many transcription factors are involved in regulating gene expression in response to neuronal activity, allowing us to learn, remember and make complex decisions. Here we review some of the recent findings that have uncovered the molecular mechanisms that underpin the control of gene regulatory networks within the nervous system. We highlight some recent insights into the gene-regulatory circuits in the development and differentiation of cells within the nervous system and discuss some of the mechanisms by which synaptic transmission influences transcription-factor activity in the mature nervous system. Mutations in genes that are important in epigenetic regulation (by influencing DNA methylation and post-translational histone modifications) have long been associated with neuronal disorders in humans such as Rett syndrome, Huntington's disease and some forms of mental retardation, and recent work has focused on unravelling their mechanisms of action. Finally, the discovery of microRNAs has produced a paradigm shift in gene expression, and we provide some examples and discuss the contribution of microRNAs to maintaining dynamic gene regulatory networks in the brain. [ABSTRACT FROM AUTHOR]

Many human diseases are the result of inappropriate changes in gene expression resulting in deleterious phenotypes of specific cells. For example, loss of expression of tumour suppressors and/or ectopic expression of oncogenes underlie many cancers, a switch from an adult to a fetal gene-expression profile in cardiac myocytes results in cardiac hypertrophy and changes in the expression of many ion channel genes leads to a phenotypic switch from contractile to proliferative smooth muscle cells in vascular diseases such as neointimal hyperplasia and atherosclerosis. Understanding the molecular mechanisms responsible for these changes in gene expression is a major goal, in order to identify novel therapeutic targets. [ABSTRACT FROM AUTHOR]