In:
PLOS Biology, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2020-11-23), p. e3000976-
Abstract:
Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal magnetic resonance imaging (MRI) in n = 292 healthy newborn infants (mean age at birth = 39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation ( n = 156 samples from 16 brains, aged 12 to 37 postconceptional weeks [pcw]). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n = 64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis (PCA) of 6 measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated with estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons, and engaged in stem cell differentiation, neuron migration, and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3000976
DOI:
10.1371/journal.pbio.3000976.g001
DOI:
10.1371/journal.pbio.3000976.g002
DOI:
10.1371/journal.pbio.3000976.g003
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10.1371/journal.pbio.3000976.g004
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10.1371/journal.pbio.3000976.g005
DOI:
10.1371/journal.pbio.3000976.g006
DOI:
10.1371/journal.pbio.3000976.g007
DOI:
10.1371/journal.pbio.3000976.s001
DOI:
10.1371/journal.pbio.3000976.s002
DOI:
10.1371/journal.pbio.3000976.s003
DOI:
10.1371/journal.pbio.3000976.s004
DOI:
10.1371/journal.pbio.3000976.s005
DOI:
10.1371/journal.pbio.3000976.s006
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10.1371/journal.pbio.3000976.s007
DOI:
10.1371/journal.pbio.3000976.s008
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10.1371/journal.pbio.3000976.s009
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10.1371/journal.pbio.3000976.s010
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10.1371/journal.pbio.3000976.s011
DOI:
10.1371/journal.pbio.3000976.s012
DOI:
10.1371/journal.pbio.3000976.s013
DOI:
10.1371/journal.pbio.3000976.s014
DOI:
10.1371/journal.pbio.3000976.s015
DOI:
10.1371/journal.pbio.3000976.s016
DOI:
10.1371/journal.pbio.3000976.s017
DOI:
10.1371/journal.pbio.3000976.s018
DOI:
10.1371/journal.pbio.3000976.s019
DOI:
10.1371/journal.pbio.3000976.s020
DOI:
10.1371/journal.pbio.3000976.s021
DOI:
10.1371/journal.pbio.3000976.s022
DOI:
10.1371/journal.pbio.3000976.s023
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2126773-X
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