scholarly journals Spatio-Temporal Roles of ASD-Associated Variants in Human Brain Development

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 535
Author(s):  
Yujin Kim ◽  
Joon-Yong An
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
De Novo ◽  
Autism Spectrum ◽  
Network Analyses ◽  
Regulatory Variants ◽  
Human Brain Development ◽  
Early Brain Development ◽  
Spatio Temporal

Transcriptional regulation of the genome arguably provides the basis for the anatomical elaboration and dynamic operation of the human brain. It logically follows that genetic variations affecting gene transcription contribute to mental health disorders, including autism spectrum disorder (ASD). A number of recent studies have shown the role of de novo variants (DNVs) in disrupting early neurodevelopment. However, there is limited knowledge concerning the role of inherited variants during the early brain development of ASD. In this study, we investigate the role of rare inherited variations in neurodevelopment. We conducted co-expression network analyses using an anatomically comprehensive atlas of the developing human brain and examined whether rare coding and regulatory variants, identified from our genetic screening of Australian families with ASD, work in different spatio-temporal functions.

La psicoterapia ericksoniana e la neurobiologia delle relazioni (prima parte)

IPNOSI ◽  
2012 ◽  
pp. 5-16
Author(s):  
Renzo Balugani
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Therapeutic Process ◽  
Clinical Context ◽  
Ecological Characteristics ◽  
Relational Perspective ◽  
Human Brain Development ◽  
Key Issues ◽  
The Mind

The mind-body relationship can be properly understood just in the light of a relational perspective of the human brain development. This article reviews key issues as perception, consciousness, empathy, mentalisation and their relational foundation: the aim is to discuss the role of those ecological characteristics in the clinical context in general, and in the Ericksonian therapeutic process in particular.

scholarly journals Postzygotic and germinal de novo mutations in ASD: exploring their biological role

2020 ◽  
Author(s):  
A Alonso-González ◽  
M Calaza ◽  
J Amigo ◽  
J González-Peñas ◽  
Martínez-Regueiro ◽  
...  
Keyword(s):  
De Novo ◽  
Autism Spectrum ◽  
Published Data ◽  
De Novo Mutations ◽  
Strong Source ◽  
Bioinformatic Approaches ◽  
Spatio Temporal ◽  
Postzygotic Mutations ◽  
Go Terms

ABSTRACTDe novo mutations (DNMs), including germinal and postzygotic mutations (PZMs), are a strong source of causality for Autism Spectrum Disorder (ASD). However, the biological processes involved behind them remain unexplored. Our aim was to detect DNMs (germinal and PZMs) in a Spanish ASD cohort (360 trios) and to explore their role across different biological hierarchies (gene, biological pathway, cell and brain areas) using bioinformatic approaches. For the majority of the analysis, a combined cohort (N=2171 trios) with ASC (Autism Sequencing Consortium) previously published data was created. New plausible candidate genes for ASD such as FMR1 and NFIA were found. In addition, genes harboring PZMs were significantly enriched for miR-137 targets in comparison with germinal DNMs that were enriched in GO terms related to synaptic transmission. The expression pattern of genes with PZMs was restricted to early mid-fetal cortex. In contrast, the analysis of genes with germinal DNMs revealed a spatio-temporal window from early to mid-fetal development stages, with expression in the amygdala, cerebellum, cortex and striatum. These results provide evidence of the pathogenic role of PZMs and suggest the existence of distinct mechanisms between PZMs and germinal DNMs that are influencing ASD risk.

scholarly journals FASN-dependent de novo lipogenesis is required for brain development

2022 ◽  
Vol 119 (2) ◽  
pp. e2112040119
Author(s):  
Daniel Gonzalez-Bohorquez ◽  
Isabel M. Gallego López ◽  
Baptiste N. Jaeger ◽  
Sibylle Pfammatter ◽  
Megan Bowers ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Cell Polarity ◽  
Fatty Acid Synthase ◽  
Radial Glia ◽  
De Novo ◽  
Building Blocks ◽  
De Novo Lipogenesis ◽  
Mammalian Brain

Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors and reduced progenitor proliferation. Furthermore, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell–derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity in human brain organoids. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor-cell polarity and lipid metabolism.

scholarly journals §Using organoids to study human brain development and evolution

2021 ◽  
Author(s):  
Wai‐Kit Chan ◽  
Rana Fetit ◽  
Rosie Griffiths ◽  
Helen Marshall ◽  
John O Mason ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Development And Evolution

scholarly journals Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

2021 ◽  
Author(s):  
Ugomma C. Eze ◽  
Aparna Bhaduri ◽  
Maximilian Haeussler ◽  
Tomasz J. Nowakowski ◽  
Arnold R. Kriegstein
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Radial Glia ◽  
Cortical Development ◽  
Cell Types ◽  
Human Cortex ◽  
Early Stages ◽  
Human Brain Development ◽  
Neuroepithelial Cells

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

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