About this Research Topic
Regulation of gene expression is a multi-layered process – from transcription to translation, including regulatory pathways such as epigenetics, chromatin remodeling and splicing, to name a few. A long-standing question in cellular and molecular neuroscience is the establishment of causality between gene expression and neurophysiology. One way to understand causality is to visualize the dynamic behavior of mRNAs and proteins in their native context and in response to neuronal activity. While transcriptomic and proteomic approaches have been the methods of choice to study genome-wide changes in neuronal gene expression, the “when and where” aspects are lost during biochemical extraction, providing only ensemble measurements. To address such spatio-temporal challenges, fluorescence imaging provides the means to image every step of gene expression and follow mRNAs and proteins from production all the way to decay. A number of these imaging technologies have been extended to single molecule and super-resolution, providing the capability to measure the copy number and location of RNAs and proteins in individual neurons.
Neuronal gene expression is an example of exquisite spatio-temporal control. This is accomplished through different gene regulatory pathways in distinct subcellular domains along the length of axons and dendrites. Using imaging, it is possible to observe mRNA localization, and protein synthesis, in different neuronal compartments and measure their temporal dynamics during activity. This is particularly important in establishing how local gene expression is essential for processes like axon guidance, network formation and synaptic plasticity. The spatio-temporal aspects of gene regulation are also being addressed from the standpoint of long distance communication in neurons, i.e. activity-dependent synapse to nucleus signaling. For example, fluorescence labeling of transcription factors demonstrated that while some transcription factors are locally translated in dendrites and travel back to the nucleus, others operate at shorter time scales in the nucleus by increased binding to specific genomic locations, and thereby regulate activity-dependent transcriptional responses. Furthermore, there have been a considerable number of attempts to elucidate how other RNA regulatory pathways like non-coding RNAs, microRNAs, RNA binding proteins and splicing machinery alter local gene expression. Dysregulation of these pathways can lead to aberrant gene expression patterns and has been associated with a number of neurodevelopmental and neuropsychiatric impairments like dementia, autism spectrum disorders, and mental retardation. It is therefore becoming increasingly important to uncover the molecular basis for the genetic forms of these cognitive disorders and to identify how activity-regulated signaling is altered. To this end, fluorescence imaging, including optogenetic manipulation of signaling pathways, provides a tremendous boost in the field of molecular neuroscience, whereby we are now beginning to understand the molecular interplay in the context of gene expression with respect to space and time.
In this Research Topic, we aim to bring together original research and review articles that elucidate the causality between gene expression and functional/structural plasticity of neurons in health and disease using imaging, and that also encompass new imaging methods and photo-manipulation techniques to investigate neuronal gene expression.
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