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Gene Regulation in Brain Development and Physiology
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Gene Regulation in Brain Development and Physiology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 16556

Special Issue Editors

Dr. Francesco Bedogni

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Guest Editor
Neuroscience and Mental Health Research Institute (NMHRI), Cardiff University, Cardiff, UK
Interests: developmental neuroscience; cerebral cortex development; molecular biology; stem cell biology; epigenetics; neurobiology and brain physiology; gene regulation
Dr. Rebecca Hodge

E-Mail Website
Guest Editor
Allen Institute for Brain Science, Seattle, WA, USA
Interests: developmental neuroscience; molecular biology; genomics; stem cell biology; human cell types
Dr. Filippo Casoni

E-Mail Website1 Website2
Guest Editor
Division of Neuroscience, San Raffaele Scientific Institute, San Raffaele University, Milan, Italy
Interests: neuroscience; neurodevelopmental biology; morphology; gene regulation; transcription factor; molecular biology

Special Issue Information

Dear Colleagues, 

Cerebral functions in adulthood rely on proper establishment and maturation of the different cellular types populating the brain. These developmental events take place during early pre- and post-natal life thanks to the activation of transcriptional programs that dictate the fate of any cell, including neurons and glial cells. The refinement of each cell’s fate requires the concerted regulation in time and space of different molecular mechanisms that affect each stage of development, from proliferation of progenitors to postmitotic cells’ migration, maturation, and integration into functional networks. Thanks to the refinement of approaches such as single cell assessments, the picture of how developmental dynamics lead to the maturation of specific cellular types is now much clearer compared to the past. Based on such knowledge it is possible to dissect how transcriptional events intrinsically regulated within each cell integrate with cues related to the environment, and thus predict how conditions such as maternal inflammation, stress and obesity can impact brain development in the offspring, and their consequences in adulthood. Eventually, this knowledge can shed new light on how differences in dynamics of brain development contribute to structural and functional differences between species. The articles collected in this special issue are focused on recent advancement in the description of these early events, and their consequences on brain functions in adulthood.

Dr. Francesco Bedogni
Dr. Rebecca Hodge
Dr. Filippo Casoni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • brain development
  • brain functions
  • transcriptional programs
  • neurons cells
  • glial cells
  • gene editing

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Published Papers (3 papers)

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Research

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12 pages, 936 KiB  
Article
The Association of Hippocampal Long-Term Potentiation-Induced Gene Expression with Genetic Risk for Psychosis
by Natalie L. Wellard, Nicholas E. Clifton, Elliott Rees, Kerrie L. Thomas and Jeremy Hall
Int. J. Mol. Sci. 2024, 25(2), 946; https://doi.org/10.3390/ijms25020946 - 12 Jan 2024
Viewed by 1505
Abstract
Genomic studies focusing on the contribution of common and rare genetic variants of schizophrenia and bipolar disorder support the view that substantial risk is conferred through molecular pathways involved in synaptic plasticity in the neurons of cortical and subcortical brain regions, including the [...] Read more.
Genomic studies focusing on the contribution of common and rare genetic variants of schizophrenia and bipolar disorder support the view that substantial risk is conferred through molecular pathways involved in synaptic plasticity in the neurons of cortical and subcortical brain regions, including the hippocampus. Synaptic long-term potentiation (LTP) is central to associative learning and memory and depends on a pattern of gene expression in response to neuronal stimulation. Genes related to the induction of LTP have been associated with psychiatric genetic risk, but the specific cell types and timepoints responsible for the association are unknown. Using published genomic and transcriptomic datasets, we studied the relationship between temporally defined gene expression in hippocampal pyramidal neurons following LTP and enrichment for common genetic risk for schizophrenia and bipolar disorder, and for copy number variants (CNVs) and de novo coding variants associated with schizophrenia. We observed that upregulated genes in hippocampal pyramidal neurons at 60 and 120 min following LTP induction were enriched for common variant association with schizophrenia and bipolar disorder subtype I. At 60 min, LTP-induced genes were enriched in duplications from patients with schizophrenia, but this association was not specific to pyramidal neurons, perhaps reflecting the combined effects of CNVs in excitatory and inhibitory neuron subtypes. Gene expression following LTP was not related to enrichment for de novo coding variants from schizophrenia cases. Our findings refine our understanding of the role LTP-related gene sets play in conferring risk to conditions causing psychosis and provide a focus for future studies looking to dissect the molecular mechanisms associated with this risk. Full article
(This article belongs to the Special Issue Gene Regulation in Brain Development and Physiology)
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13 pages, 4655 KiB  
Article
Single-Cell Transcriptomics Reveals Conserved Regulatory Networks in Human and Mouse Interneuron Development
by Francesca Keefe, Jimena Monzón-Sandoval, Anne E. Rosser, Caleb Webber and Meng Li
Int. J. Mol. Sci. 2023, 24(9), 8122; https://doi.org/10.3390/ijms24098122 - 1 May 2023
Cited by 9 | Viewed by 2794
Abstract
Inhibitory GABAergic interneurons originate in the embryonic medial ganglionic eminence (MGE) and control network activity in the neocortex. Dysfunction of these cells is believed to lead to runaway excitation underlying seizure-based neurological disorders such as epilepsy, autism, and schizophrenia. Despite their importance in [...] Read more.
Inhibitory GABAergic interneurons originate in the embryonic medial ganglionic eminence (MGE) and control network activity in the neocortex. Dysfunction of these cells is believed to lead to runaway excitation underlying seizure-based neurological disorders such as epilepsy, autism, and schizophrenia. Despite their importance in heath and disease, our knowledge about the development of this diverse neuronal population remains incomplete. Here we conducted single-cell RNA sequencing (scRNA-seq) of human foetal MGE from 10 to 15 weeks post conception. These MGE tissues are composed of largely cycling progenitors and immature post-mitotic interneurons with characteristic regional marker expression. Analysis of integrated human and mouse MGE data revealed species-conserved transcriptomic profiles and regulatory programs. Moreover, we identified novel candidate transcription regulators for human interneuron differentiation. These findings provide a framework for in vitro modelling of interneuron development and a strategy for potentially enhancing interneuron production from human pluripotent stem cells. Full article
(This article belongs to the Special Issue Gene Regulation in Brain Development and Physiology)
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Review

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17 pages, 893 KiB  
Review
Extracellular Matrix Regulation in Physiology and in Brain Disease
by Alyssa Soles, Adem Selimovic, Kaelin Sbrocco, Ferris Ghannoum, Katherine Hamel, Emmanuel Labrada Moncada, Stephen Gilliat and Marija Cvetanovic
Int. J. Mol. Sci. 2023, 24(8), 7049; https://doi.org/10.3390/ijms24087049 - 11 Apr 2023
Cited by 30 | Viewed by 11244
Abstract
The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss [...] Read more.
The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss the physiological roles of the ECM and its contribution to the pathogenesis of brain disease, highlighting the gene expression changes, transcriptional factors involved, and a role for microglia in ECM regulation. Much of the research conducted thus far on disease states has focused on “omic” approaches that reveal differences in gene expression related to the ECM. Here, we review recent findings on alterations in the expression of ECM-associated genes in seizure, neuropathic pain, cerebellar ataxia, and age-related neurodegenerative disorders. Next, we discuss evidence implicating the transcription factor hypoxia-inducible factor 1 (HIF-1) in regulating the expression of ECM genes. HIF-1 is induced in response to hypoxia, and also targets genes involved in ECM remodeling, suggesting that hypoxia could contribute to ECM remodeling in disease conditions. We conclude by discussing the role microglia play in the regulation of the perineuronal nets (PNNs), a specialized form of ECM in the central nervous system. We show evidence that microglia can modulate PNNs in healthy and diseased brain states. Altogether, these findings suggest that ECM regulation is altered in brain disease, and highlight the role of HIF-1 and microglia in ECM remodeling. Full article
(This article belongs to the Special Issue Gene Regulation in Brain Development and Physiology)
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