Molecular Mechanisms Underlying Neurogenic Programs

About this Research Topic

Background

The cerebral cortex is one of the most complex structures in the body comprising different classes of neurons and glial cells. In mammals, and especially in humans, the embryonic development of cerebral cortices is a highly coordinated process that requires precise spatiotemporal transcriptional regulation leading to different cortical cell populations. Owing to the recent technical advancement, it became possible to investigate the early gene-regulatory activities and the molecular mechanisms responsible for generating different types of neural progenitor cells (NPCs) in the developing human brain, which later expand in number and eventually differentiate to neurons. These newborn neurons elongate their neurites toward their targets using complex molecular signaling released by the neighboring cells or by the local environment.

A wealth of recent experimental data indicates that, besides axoplasmic flow, the axonal system of protein synthesis plays a key role in axonal pathfinding, allowing a rapid and subtle modulation of the proteome in the individual axonal branches. Although remodeling the synaptic regions in response to the external stimuli serves as an important mechanism responsible for the proper brain development, deregulated synaptic plasticity is associated with both neurodevelopmental and neuropsychiatric disorders. Furthermore, during the development of brain cortices, contributions are also likely to be made by epigenetic modifications of the gene networks and posttranslational changes of the proteins being associated with synaptic plasticity. Insights into such mechanisms would enrich our understanding of the altered cellular and molecular events that are involved in these neural disorders.

Although much of our knowledge of brain cortex development has been gained from the studies on animal models, large gaps remain in our understanding of the molecular mechanisms that control human cortical development. Interestingly, many aspects of corticogenesis can be recapitulated in vitro from mouse and human embryonic stem cells, or from induced pluripotent stem cells (iPSCs), by use of a variety of experimental systems from 2D models to organoids 3D. Thus, the approach utilizing the latter experimental tools, provides us with a novel and powerful model in which to study human corticogenesis. In addition, the possibility to reprogram the cells obtained from patients into iPSCs that can be used to generate 2D and 3D cultures, opens new avenues toward the comprehension of altered neurogenic program in neurodevelopmental and neuropsychiatric pathologies with important implications for diagnosis and treatment of these diseases.

In the given context, this Research Topic aims to highlight the current advances of our knowledge on the molecular and cellular processes driving neurogenesis during brain cortex development, as well as to describe how these processes are altered in neurodevelopmental and neuropsychiatric disease. We welcome any articles addressing this research topic in a multidisciplinary approach involving molecular biology, biochemistry, cell biology, bioinformatics and neurobiology methodologies.

The themes covered include but are not limited to:

• Molecular mechanisms underlying brain cortex development; transcriptomic and proteomic signatures of specific cell types, or at single-cell level in wild type or pathological conditions.
• Epigenetic aspects of cellular identity or reprogramming.
• Molecular mechanisms underlying synaptic plasticity during development of the brain cortex.

Keywords: single cells, bulk RNA-seq, epigenomics, synaptic plasticity, disease, reprogramming

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