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Cortical morphology at birth reflects spatio-temporal patterns of gene expression in the fetal brain

View ORCID ProfileG. Ball, View ORCID ProfileJ. Seidlitz, J. O’Muircheartaigh, R. Dimitrova, D. Fenchel, A. Makropoulos, D. Christiaens, A. Schuh, J. Passerat-Palmbach, L. Cordero-Grande, E. Hughes, A. Price, J.V. Hajnal, D. Rueckert, E.C. Robinson, A.D. Edwards
doi: https://doi.org/10.1101/2020.01.28.922849
G. Ball
Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, AustraliaCentre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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  • ORCID record for G. Ball
  • For correspondence: gareth.ball@mcri.edu.au
J. Seidlitz
Developmental Neurogenomics Unit, National Institute of Mental Health, Bethesda, USADepartment of Psychiatry, University of Cambridge, UK
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J. O’Muircheartaigh
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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R. Dimitrova
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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D. Fenchel
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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A. Makropoulos
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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D. Christiaens
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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A. Schuh
Biomedical Image Analysis Group, Department of Computing, Imperial College London, UK
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J. Passerat-Palmbach
Biomedical Image Analysis Group, Department of Computing, Imperial College London, UK
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L. Cordero-Grande
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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E. Hughes
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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A. Price
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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J.V. Hajnal
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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D. Rueckert
Biomedical Image Analysis Group, Department of Computing, Imperial College London, UK
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E.C. Robinson
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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A.D. Edwards
Centre for the Developing Brain, Department of Perinatal Imaging & Health, King’s College London, UK
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Abstract

In this study, we test the hypothesis that noninvasive markers of brain development reflect the spatiotemporal patterning of genes underlying corticogenesis during gestation and the developmental staging of the neonatal brain. Additionally, we test the selective vulnerability of molecular processes underlying cortical development to disruption following preterm birth. We find that gene expression in the fetal cortex is mirrored by a principal mode of variation in the neonatal cortex. Specifically, regional variation in cortical morphology and microstructure reflect differences in developmental maturity across cortical areas, indexed by the differential timing of gene expression across multiple cell types in the fetal cortex. Further, the effects of preterm birth are temporally and spatially coincident to developmental processes involving the differentiation and specialisation of cortical oligodendrocyte populations. This work provides an experimental framework to link molecular developmental mechanisms to macroscopic measures of cortical anatomy in early life, demonstrating the relationship between fetal gene expression and neonatal brain development and highlighting the specific impact of early exposure to the extrauterine environment due to preterm birth.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted January 29, 2020.
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Cortical morphology at birth reflects spatio-temporal patterns of gene expression in the fetal brain
G. Ball, J. Seidlitz, J. O’Muircheartaigh, R. Dimitrova, D. Fenchel, A. Makropoulos, D. Christiaens, A. Schuh, J. Passerat-Palmbach, L. Cordero-Grande, E. Hughes, A. Price, J.V. Hajnal, D. Rueckert, E.C. Robinson, A.D. Edwards
bioRxiv 2020.01.28.922849; doi: https://doi.org/10.1101/2020.01.28.922849
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Cortical morphology at birth reflects spatio-temporal patterns of gene expression in the fetal brain
G. Ball, J. Seidlitz, J. O’Muircheartaigh, R. Dimitrova, D. Fenchel, A. Makropoulos, D. Christiaens, A. Schuh, J. Passerat-Palmbach, L. Cordero-Grande, E. Hughes, A. Price, J.V. Hajnal, D. Rueckert, E.C. Robinson, A.D. Edwards
bioRxiv 2020.01.28.922849; doi: https://doi.org/10.1101/2020.01.28.922849

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