Molecular signatures of cortical expansion in the human fetal brain.

Autor:	Ball G; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Australia., Oldham S; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Australia., Kyriakopoulou V; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Williams LZJ; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Karolis V; Centre for the Developing Brain, King's College London, London, UK.; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Price A; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Hutter J; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Seal ML; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Australia., Alexander-Bloch A; Department of Child and Adolescent Psychiatry and Behavioral Sciences, The Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA.; Lifespan Brain Institute, The Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, PA.; Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA., Hajnal JV; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Edwards AD; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Robinson EC; Centre for the Developing Brain, King's College London, London, UK.; School of Biomedical Engineering & Imaging Science, King's College London, London, UK., Seidlitz J; Department of Child and Adolescent Psychiatry and Behavioral Sciences, The Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA.; Lifespan Brain Institute, The Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, PA.; Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 13. Date of Electronic Publication: 2024 Feb 13.
DOI:	10.1101/2024.02.13.580198
Abstrakt:	The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. A growing catalogue of cells in the prenatal brain has revealed remarkable molecular diversity across cortical areas. 1,2 Despite this, little is known about how this translates into the patterns of differential cortical expansion observed in humans during the latter stages of gestation. Here we present a new resource, μBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal developing brain. Built using generative artificial intelligence, μBrain is a three-dimensional cellular-resolution digital atlas combining publicly-available serial sections of the postmortem human brain at 21 weeks gestation 3 with bulk tissue microarray data, sampled across 29 cortical regions and 5 transient tissue zones. 4 Using μBrain, we evaluate the molecular signatures of preferentially-expanded cortical regions during human gestation, quantified in utero using magnetic resonance imaging (MRI). We find that differences in the rates of expansion across cortical areas during gestation respect anatomical and evolutionary boundaries between cortical types 5 and are founded upon extended periods of upper-layer cortical neuron migration that continue beyond mid-gestation. We identify a set of genes that are upregulated from mid-gestation and highly expressed in rapidly expanding neocortex, which are implicated in genetic disorders with cognitive sequelae. Our findings demonstrate a spatial coupling between areal differences in the timing of neurogenesis and rates of expansion across the neocortical sheet during the prenatal epoch. The μBrain atlas is available from: https://garedaba.github.io/micro-brain/ and provides a new tool to comprehensively map early brain development across domains, model systems and resolution scales. Competing Interests: Conflicts of interest JS and AFA-B are co-founders of Centile Bioscience.
Databáze:	MEDLINE
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