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Typical development of the human fetal subplate: Regional heterogeneity, growth, and asymmetry assessed by in vivo T2-weighted MRI.

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Title: Typical development of the human fetal subplate: Regional heterogeneity, growth, and asymmetry assessed by in vivo T2-weighted MRI.
Authors: Gondová, Andrea1,2 andrea.gondova@childrens.harvard.edu, Zhang, Jennings1,2, You, Sungmin1,2, Jeong, Seungyoon1,2, Candela-Leal, Milton Osiel1, Rollins, Caitlin Kantrowitz3, Grant, Patricia Ellen1,2,4, Yun, Hyuk Jin1,2, Im, Kiho1,2,5
Source: Proceedings of the National Academy of Sciences of the United States of America. 4/14/2026, Vol. 123 Issue 15, p1-12. 35p.
Subjects: Fetal brain, Cerebral cortex development, Symmetry (Biology), Brain anatomy, Spatial variation, Magnetic resonance imaging
Abstract: The subplate (SP) is a transient fetal brain compartment supporting neuronal migration, axonal ingrowth, and early cortical activity, yet the dynamics of its regional development remain poorly understood in vivo. Using T2-weighted fetal MRI of 68 typically developing fetuses (22 to 32 wk gestational age, GA), we developed a semiautomated pipeline to quantify regional SP morphology (thickness, surface area, and volume). SP characteristics scaled strongly with GA and residual brain volume and showed marked regional differences. After correcting for geometric confounds, regional variation of SP thickness persisted, with highest values in parietal and perisylvian regions, suggesting that SP thickness may serve as a sensitive marker of intrinsic developmental differences. Between the late 2nd and early 3rd trimesters, mean SP thickness increased by 39.2% with large variation across regions (±11.0 SD), whereas surface area growth was more uniform (64.3% ±0.7 SD). Continuous growth trajectories clustered into distinct spatiotemporal profiles: early-developing regions (e.g., pericentral and medial occipital cortices) contrasted with later-developing regions (prefrontal, temporal, and parietal cortices). These patterns partially recapitulate primary-to-association, medial-to-lateral, and posterior-to-anterior maturational hierarchies, pointing to organized developmental programs. SP development also showed region-specific hemispheric asymmetries, including leftward thickness and volume asymmetry in the superior temporal and precentral gyri. Some asymmetries amplified, others attenuated or reversed with age, suggesting both transient states and potential precursors of postnatal lateralization. Together, these findings provide a framework for regional SP quantification and position SP morphology, particularly thickness, as a promising early biomarker that might link fetal SP changes to subsequent cortical development and neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Typical development of the human fetal subplate: Regional heterogeneity, growth, and asymmetry assessed by in vivo T2-weighted MRI.
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  Data: <searchLink fieldCode="AR" term="%22Gondová%2C+Andrea%22">Gondová, Andrea</searchLink><relatesTo>1,2</relatesTo><i> andrea.gondova@childrens.harvard.edu</i><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Jennings%22">Zhang, Jennings</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22You%2C+Sungmin%22">You, Sungmin</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Jeong%2C+Seungyoon%22">Jeong, Seungyoon</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Candela-Leal%2C+Milton+Osiel%22">Candela-Leal, Milton Osiel</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Rollins%2C+Caitlin+Kantrowitz%22">Rollins, Caitlin Kantrowitz</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Grant%2C+Patricia+Ellen%22">Grant, Patricia Ellen</searchLink><relatesTo>1,2,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Yun%2C+Hyuk+Jin%22">Yun, Hyuk Jin</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Im%2C+Kiho%22">Im, Kiho</searchLink><relatesTo>1,2,5</relatesTo>
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  Data: <searchLink fieldCode="DE" term="%22Fetal+brain%22">Fetal brain</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebral+cortex+development%22">Cerebral cortex development</searchLink><br /><searchLink fieldCode="DE" term="%22Symmetry+%28Biology%29%22">Symmetry (Biology)</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+anatomy%22">Brain anatomy</searchLink><br /><searchLink fieldCode="DE" term="%22Spatial+variation%22">Spatial variation</searchLink><br /><searchLink fieldCode="DE" term="%22Magnetic+resonance+imaging%22">Magnetic resonance imaging</searchLink>
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  Data: The subplate (SP) is a transient fetal brain compartment supporting neuronal migration, axonal ingrowth, and early cortical activity, yet the dynamics of its regional development remain poorly understood in vivo. Using T2-weighted fetal MRI of 68 typically developing fetuses (22 to 32 wk gestational age, GA), we developed a semiautomated pipeline to quantify regional SP morphology (thickness, surface area, and volume). SP characteristics scaled strongly with GA and residual brain volume and showed marked regional differences. After correcting for geometric confounds, regional variation of SP thickness persisted, with highest values in parietal and perisylvian regions, suggesting that SP thickness may serve as a sensitive marker of intrinsic developmental differences. Between the late 2nd and early 3rd trimesters, mean SP thickness increased by 39.2% with large variation across regions (±11.0 SD), whereas surface area growth was more uniform (64.3% ±0.7 SD). Continuous growth trajectories clustered into distinct spatiotemporal profiles: early-developing regions (e.g., pericentral and medial occipital cortices) contrasted with later-developing regions (prefrontal, temporal, and parietal cortices). These patterns partially recapitulate primary-to-association, medial-to-lateral, and posterior-to-anterior maturational hierarchies, pointing to organized developmental programs. SP development also showed region-specific hemispheric asymmetries, including leftward thickness and volume asymmetry in the superior temporal and precentral gyri. Some asymmetries amplified, others attenuated or reversed with age, suggesting both transient states and potential precursors of postnatal lateralization. Together, these findings provide a framework for regional SP quantification and position SP morphology, particularly thickness, as a promising early biomarker that might link fetal SP changes to subsequent cortical development and neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1073/pnas.2528620123
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      – SubjectFull: Symmetry (Biology)
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      – SubjectFull: Brain anatomy
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      – SubjectFull: Spatial variation
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              Text: 4/14/2026
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