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 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.

Data availability

Developing Human Connectome project data is open-access and available for download following completion of a data-usage agreement via: http://www.developingconnectome.org/. Data will also be available at: https://nda.nih.gov/edit_collection.html?id=3955

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Sian Wilson

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4617-3583
  2. Maximilian Pietsch

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Lucilio Cordero-Grande

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Daan Christiaens

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Alena Uus

    Department of Biomedical Engineering, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Vyacheslav R Karolis

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Vanessa Kyriakopoulou

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Kathleen Colford

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Anthony N Price

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Jana Hutter

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Mary A Rutherford

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Emer J Hughes

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Serena J Counsell

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8033-5673
  14. Jacques-Donald Tournier

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Joseph V Hajnal

    Centre for the Developing Brain, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. A David Edwards

    Department of Biomedical Engineering, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4801-7066
  17. Jonathan O'Muicheartaigh

    Centre for the Developing Brain, King's College London, London, United Kingdom
    For correspondence
    jonathanom@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  18. Tomoki Arichi

    Centre for the Developing Brain, King's College London, London, United Kingdom
    For correspondence
    tomoki.arichi@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3550-1644

Funding

European Research Council (Seventh Framework Programme: FP/2007/2013)

  • Maximilian Pietsch
  • Lucilio Cordero-Grande
  • Daan Christiaens
  • Vyacheslav R Karolis
  • Vanessa Kyriakopoulou
  • Anthony N Price
  • Jana Hutter
  • Emer J Hughes
  • Jacques-Donald Tournier
  • Joseph V Hajnal
  • A David Edwards

Wellcome Trust (Sir Henry Dale Fellowship: 206675/Z/17/Z)

  • Jonathan O'Muicheartaigh

Medical Research Council Centre for Neurodevelopmental Disorders (MR/N0266063/1)

  • Sian Wilson
  • Mary A Rutherford
  • A David Edwards
  • Jonathan O'Muicheartaigh
  • Tomoki Arichi

Medical Research Council (Translation support fellowship: MR/V036874/1)

  • Vyacheslav R Karolis
  • Tomoki Arichi

Wellcome / EPSRC Centre for Biomedical Engineering, Kings College London (WT 203148/Z/16/Z)

  • Anthony N Price
  • Jana Hutter
  • Jacques-Donald Tournier
  • Joseph V Hajnal

Medical Research Council (Clinician Scientist Fellowship MR/P008712/1)

  • Tomoki Arichi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was approved by the UK Health Research Authority (Research Ethics Committee reference number: 14/LO/1169) and written parental consent was obtained in every case for imaging and open data release of the anonymized data.

Copyright

© 2023, Wilson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,217
    views
  • 223
    downloads
  • 19
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sian Wilson
  2. Maximilian Pietsch
  3. Lucilio Cordero-Grande
  4. Daan Christiaens
  5. Alena Uus
  6. Vyacheslav R Karolis
  7. Vanessa Kyriakopoulou
  8. Kathleen Colford
  9. Anthony N Price
  10. Jana Hutter
  11. Mary A Rutherford
  12. Emer J Hughes
  13. Serena J Counsell
  14. Jacques-Donald Tournier
  15. Joseph V Hajnal
  16. A David Edwards
  17. Jonathan O'Muicheartaigh
  18. Tomoki Arichi
(2023)
Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain
eLife 12:e83727.
https://doi.org/10.7554/eLife.83727

Share this article

https://doi.org/10.7554/eLife.83727

Further reading

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.

    1. Developmental Biology
    Jing Lu, Hao Xu ... Kai Lei
    Tools and Resources

    The intricate coordination of the neural network in planarian growth and regeneration has remained largely unrevealed, partly due to the challenges of imaging the CNS in three dimensions (3D) with high resolution and within a reasonable timeframe. To address this gap in systematic imaging of the CNS in planarians, we adopted high-resolution, nanoscale imaging by combining tissue expansion and tiling light-sheet microscopy, achieving up to fourfold linear expansion. Using an automatic 3D cell segmentation pipeline, we quantitatively profiled neurons and muscle fibers at the single-cell level in over 400 wild-type planarians during homeostasis and regeneration. We validated previous observations of neuronal cell number changes and muscle fiber distribution. We found that the increase in neuron cell number tends to lag behind the rapid expansion of somatic cells during the later phase of homeostasis. By imaging the planarian with up to 120 nm resolution, we also observed distinct muscle distribution patterns at the anterior and posterior poles. Furthermore, we investigated the effects of β-catenin-1 RNAi on muscle fiber distribution at the posterior pole, consistent with changes in anterior-posterior polarity. The glial cells were observed to be close in contact with dorsal-ventral muscle fibers. Finally, we observed disruptions in neural-muscular networks in inr-1 RNAi planarians. These findings provide insights into the detailed structure and potential functions of the neural-muscular system in planarians and highlight the accessibility of our imaging tool in unraveling the biological functions underlying their diverse phenotypes and behaviors.