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Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain.

ABSTRACT: The development of connectivity between the thalamus and maturing cortex is a fundamental process in the second half of human gestation, establishing the neural circuits that are the basis for several important brain functions. In this study, we acquired high-resolution in utero diffusion magnetic resonance imaging (MRI) from 140 fetuses as part of the Developing Human Connectome Project, to examine the emergence of thalamocortical white matter over the second to third trimester. We delineate developing thalamocortical pathways and parcellate the fetal thalamus according to its cortical connectivity using diffusion tractography. We then quantify microstructural tissue components along the tracts in fetal compartments that are critical substrates for white matter maturation, such as the subplate and intermediate zone. We identify patterns of change in the diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester, such as the disassembly of radial glial scaffolding and the lamination of the cortical plate. These maturational trajectories of MR signal in transient fetal compartments provide a normative reference to complement histological knowledge, facilitating future studies to establish how developmental disruptions in these regions contribute to pathophysiology.

SUBMITTER: Wilson S

PROVIDER: S-EPMC10125021 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain.

Wilson Siân S Pietsch Maximilian M Cordero-Grande Lucilio L Christiaens Daan D Uus Alena A Karolis Vyacheslav R VR Kyriakopoulou Vanessa V Colford Kathleen K Price Anthony N AN Hutter Jana J Rutherford Mary A MA Hughes Emer J EJ Counsell Serena J SJ Tournier Jacques-Donald JD Hajnal Joseph V JV Edwards A David AD O'Muircheartaigh Jonathan J Arichi Tomoki T

eLife 20230403

The development of connectivity between the thalamus and maturing cortex is a fundamental process in the second half of human gestation, establishing the neural circuits that are the basis for several important brain functions. In this study, we acquired high-resolution in utero diffusion magnetic resonance imaging (MRI) from 140 fetuses as part of the Developing Human Connectome Project, to examine the emergence of thalamocortical white matter over the second to third trimester. We delineate de ...[more]

PMID: 37010273

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Project description:BackgroundTissue engineering techniques offer new strategies to understand complex processes in a controlled and reproducible system. In this study, we generated bilayered human tissue substitutes consisting of a cellular connective tissue with a suprajacent epithelium (full-thickness stromal-epithelial substitutes or SESS) and human tissue substitutes with an epithelial layer generated on top of an acellular biomaterial (epithelial substitutes or ESS). Both types of artificial tissues were studied at sequential time periods to analyze the maturation process of the extracellular matrix.ResultsRegarding epithelial layer, ESS cells showed active proliferation, positive expression of cytokeratin 5, and low expression of differentiation markers, whereas SESS epithelium showed higher differentiation levels, with a progressive positive expression of cytokeratin 10 and claudin. Stromal cells in SESS tended to accumulate and actively synthetize extracellular matrix components such as collagens and proteoglycans in the stromal area in direct contact with the epithelium (zone 1), whereas these components were very scarce in ESS. Regarding the basement membrane, ESS showed a partially differentiated structure containing fibronectin-1 and perlecan. However, SESS showed higher basement membrane differentiation, with positive expression of fibronectin 1, perlecan, nidogen 1, chondroitin-6-sulfate proteoglycans, agrin, and collagens types IV and VII, although this structure was negative for lumican. Finally, both ESS and SESS proved to be useful tools for studying metabolic pathway regulation, revealing differential activation and upregulation of the transforming growth factor-β pathway in ESS and SESS.ConclusionsThese results confirm the relevance of epithelial-stromal interaction for extracellular matrix development and differentiation, especially regarding basement membrane components, and suggest the usefulness of bilayered artificial tissue substitutes to reproduce ex vivo the extracellular matrix maturation and development process of human tissues.

Project description: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.

Dataset Information

Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain.

Publications

Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain.

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