About this Research Topic
A finely tuned regulation of gene expression is essential for shaping the nervous system and for maintaining its homeostasis throughout life. Disruptions in gene regulation can impact brain development and physiology in ways that contribute to diverse pathologies.
The master orchestrators of gene activity in the nucleus are transcription factors, proteins that recognize and bind to specific DNA motifs in regulatory regions and drive changes in gene expression. Transcription factors act with the help of other co-factor proteins, including components of the Mediator complex, histone modifying enzymes, chromatin modelers, and DNA methylases. In addition, transcription factor activity in the nervous system can be modulated by extracellular signals, including growth factors, hormones, neuropeptides and neurotransmitters that activate specific receptors and intracellular transduction pathways.
Transcriptional regulation has been studied for over 60 years. Among the many technical milestones in this period, the advent of genetically modified animal models has advanced our understanding of brain, neuronal, and glial development and function in the absence or presence of mutated forms of transcription factors and other regulatory components.
Novel RNA sequencing techniques have opened the possibility to characterize the complete transcriptome of upcoming models. Chromatin immunoprecipitation coupled to high throughput sequencing techniques has provided whole-genome profiles of transcription factors and binding sites, and histone modifications in wild-type and experimental subjects.
In addition, highly improved and sensitive single-cell transcriptomic techniques applied to neurons and other cell types, allow for an unprecedented level of detail in the characterization of experimental models.
Genome-wide and gene-centric studies have shown that every transcription regulator is part of a complex and dynamic interplay of molecular interactions, modulated by intracellular and extracellular stimuli, generating a plethora of neuronal and glial cell types throughout development, and maintaining their proper function during the lifetime of the individual.
Transcription regulation within the human nervous system must be perceived in the context of these orchestrated interactions.
For instance, it is not completely understood how certain transcription factors such as bHLH (basic helix-loop-helix), homeobox and CREB (cyclic AMP-responsive element-binding factor) family proteins, differentially mediate spatial and temporal dependent cell programs within the brain; and how cross-talk among neurons and other cell types ultimately impacts on transcriptomes, and thus on cell's phenotypes.
An in-depth understanding of the mechanisms of transcription regulation is needed in order to better describe how each element, from genes to cells, defines and maintains identities and functionalities in the healthy and diseased brain.
This Research Topic is oriented to developing an integrative view about transcription regulation within the nervous system, focusing on developmental and homeostatic processes, dysregulation in functionality and expression levels and consequent associated pathologies such as neurodevelopmental disorders, brain tumors, and neurodegenerative diseases.
Transcription regulation investigations will specifically focus on transcription factors that belong to the bHLH (e.g. NeuroD), homeobox (e.g. Islet, Pax, Rax, and Lhx) and CREB families, and on their roles over defined nervous system areas: cerebral cortex, thalamic and hypothalamic areas, interacting with the developing brain.
Specific topics are listed below:
- Transcription regulation of the nervous system ontogeny and homeostasis with focus to specific and crucial temporal windows in development, depending on the studied species.
- Structural and functional dynamics of transcription factors tuning within the changing environmental context of the central nervous system.
- Transcriptional marks guiding specific patterning for defined neuronal and glial phenotypes, and their dynamics throughout ontogeny.
- New in vivo and in vitro genetically engineered model organisms to further study and understand transcription regulation in the healthy and diseased nervous system and any potential compensatory effect.
- State-of-art technologies including single-cell and single-nucleus transcriptomics approaches, and bioinformatics, as applied to gene expression regulation within the nervous system.
Original articles, reviews, and short communications are welcome. We expect to attract significant contributions from diverse specialists in the field, in order to establish new trends for future studies.
Image credits: Estela M. Muñoz - Sagittal section of rat brain (E15) including the developing pineal gland immunoreactive for Pax6
Keywords: Transcription factor, Transcription regulation Central Nervous System, Development, Homeostasis
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