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. 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.

The functional anatomy of organisms is maintained by the coordination of different systems, that often rely on particular interactions between specialized cells and between macromolecules. The immune system works with the circulatory and the lymphatic systems to protect most of the organs. However, some organs are considered immune privileged due to the presence of highly selective and regulated barriers, such as the blood-brain barrier (BBB) within the brain. The BBB controls periphery-brain molecule exchange and prevents immune effector cells from entering the homeostatic brain. BBB-associated elements, such as endothelial cells, pericytes, astrocytes, and microglia, potentially can function as antigen-presenting cells (APC). Pathological scenarios that induce dysfunction of the BBB and its associated cells may lead to the infiltration of lymphocytes crossing over from the blood to brain. Similarly, traumas can also enable B and T lymphocytes to pass bidirectionally between the CNS and the periphery, via the meningeal lymphatic vessels which drain into the cervical lymph nodes. Research in animals and in humans has revealed that B and T cells are involved in the progression of neurological diseases. It has been showed that under particular conditions, T cells establish themselves and become resident in the brain (T RM cells), from where they can either exert beneficial or detrimental effects on brain function. Amazing efforts have been made to further comprehend interactions between brain-specific cells and peripheral immune cells, and especially their roles and impact on the onset, progression, and eventual resolution of diverse brain pathologies.