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New Genetic Atlas of Brain Development

Summary: Researchers created an atlas detailing early genetic development of the brain, from weeks 6 to 13 of embryonic growth. This new work provides a comprehensive view of gene regulation in different regions of the brain, going beyond previous studies focused primarily on the cortex.

The atlas should help understand developmental errors leading to pediatric brain tumors and could contribute to the development of targeted treatments. Additionally, the study is part of the larger Human Developmental Cell Atlas project, which aims to map the genetic development of various organs.

Highlights:

  1. In-depth brain mapping: The atlas provides a detailed map of gene activation and cell development in the brain during early embryonic stages.
  2. Potential clinical applications: Knowledge from this atlas is used to study and understand the origins of brain cancer in children, potentially leading to new therapeutic strategies.
  3. Collaborative research effort: This research is part of a larger effort, funded by prominent foundations, to create comprehensive cellular atlases for multiple organs, thereby improving our understanding of human development and disease.

Source: Karolinska Institute

In an article published in Natureresearchers from Karolinska Institutet present an atlas of early brain development.

The atlas can be used, among other things, to find out what went wrong in the development of brain tumors in children and also to find new treatments.

An international research team led by Karolinska Institutet has mapped the early genetic development of the brain and can now present an atlas of embryonic development between weeks 6 and 13.

The research was carried out using a method capable of measuring both active regions of DNA and RNA strands formed in individual cells. Credit: Neuroscience News

“This is the first comprehensive study of brain development focused on gene regulation. Previous studies have almost always focused on the cortex, or cerebral cortex. Our study is a systematic mapping of the entire brain so that all regions can be compared with each other,” explains Sten Linnarsson, professor of molecular systems biology at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and head of the research of the study.

When the brain begins to develop in the early embryo, it begins as something like a tube, the walls of which will grow to become the brain and the center of the fluid-filled tube will become the ventricles, the cavity of the brain.

Between the 6th and 13th weeks of pregnancy, rapid specialization of the cells in the walls of the tube is observed. This happens through a very complex cascade reaction in which substances are secreted that induce the first cells to grow in a certain way. These cells then secrete additional signals that control the next stage of cell development, etc.

The signals activate genes that produce proteins that specialize in different cell types and also act as new signals.

“It is this process, how, in what order and in which cell types the genes are activated during this process of brain formation that we studied. We wanted to follow the process from DNA to RNA to protein at every step,” explains Sten Linnarsson.

The research was carried out using a method capable of measuring both active regions of DNA and RNA strands formed in individual cells. The researchers then pieced together the puzzle and can now present a map of how it works.

The research is part of Sweden’s largest “Human Developmental Cell Atlas” project in which several research groups have studied the genetic development of the brain, heart, lungs, etc. Research in the project is now moving forward and researchers are using the maps to find answers to what went wrong with the disease.

“We are currently studying the occurrence of brain cancer in children. Fortunately, this is a rare disease, but among the various diseases that lead to death in children, it is one of the most common.

“We study tumors that arise during embryonic brain development and use the atlas to try to understand the mechanisms of normal development gone wrong and how this leads to the formation and growth of tumors,” explains Sten Linnarsson.

Funding: The research was funded by the Erling-Persson Family Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Foundation for Strategic Research and EC Horizon 2020. Sten Linnarsson is scientific advisor to the Center of Excellence in Immunotherapy at Moleculent, Combigene and the University of Oslo. He and first author Camiel Mannens are also shareholders in EEL Transcriptomics AB, which owns the intellectual property rights to EEL-FISH.

About this news from research in genetics and neurodevelopment

Author: Sten Linnarsson
Source: Karolinska Institute
Contact: Sten Linnarsson – Karolinska Institute
Picture: Image is credited to Neuroscience News

Original research: Free access.
“Chromatin Accessibility During First Trimester Human Neurodevelopment” by Sten Linnarsson et al. Nature


Abstract

Chromatin Accessibility During First Trimester Human Neurodevelopment

The human brain develops through a tightly organized cascade of patterning events, driven by the expression of transcription factors and changes in chromatin accessibility.

Although gene expression in the developing brain has been described with single-cell resolution, similar atlases of chromatin accessibility have primarily focused on the forebrain.

Here we describe chromatin accessibility and expression of paired genes throughout the developing human brain during the first trimester (6–13 weeks after conception).

We defined 135 clusters and used multiomics measures to link candidates cis-elements regulating gene expression. The number of accessible regions increases both with age and with neuronal differentiation.

Using a convolutional neural network, we identified putative functional transcription factor binding sites in enhancers characterizing neuronal subtypes.

We applied this model to cis-regulatory elements linked to ESRR to elucidate its activation mechanism in the Purkinje cell line.

Finally, by linking disease-associated single nucleotide polymorphisms to cis-regulatory elements, we validated putative pathogenic mechanisms in several diseases and identified midbrain-derived GABAergic neurons as being most vulnerable to major mutations linked to depressive disorder.

Our results provide a more detailed view of the key gene regulatory mechanisms underlying the emergence of brain cell types during the first trimester and a comprehensive reference for future studies related to human neurodevelopment.

News Source : neurosciencenews.com
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