Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum
The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midl...
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Elsevier
2016-10-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716312554 |
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author | Ilan Gobius Laura Morcom Rodrigo Suárez Jens Bunt Polina Bukshpun William Reardon William B. Dobyns John L.R. Rubenstein A. James Barkovich Elliott H. Sherr Linda J. Richards |
author_facet | Ilan Gobius Laura Morcom Rodrigo Suárez Jens Bunt Polina Bukshpun William Reardon William B. Dobyns John L.R. Rubenstein A. James Barkovich Elliott H. Sherr Linda J. Richards |
author_sort | Ilan Gobius |
collection | DOAJ |
description | The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis. |
first_indexed | 2024-12-13T14:40:12Z |
format | Article |
id | doaj.art-8818c85899d244be9596722d1db7333e |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-13T14:40:12Z |
publishDate | 2016-10-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
spelling | doaj.art-8818c85899d244be9596722d1db7333e2022-12-21T23:41:38ZengElsevierCell Reports2211-12472016-10-0117373574710.1016/j.celrep.2016.09.033Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus CallosumIlan Gobius0Laura Morcom1Rodrigo Suárez2Jens Bunt3Polina Bukshpun4William Reardon5William B. Dobyns6John L.R. Rubenstein7A. James Barkovich8Elliott H. Sherr9Linda J. Richards10Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, AustraliaQueensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, AustraliaQueensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, AustraliaQueensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, AustraliaDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USANational Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, IrelandCenter for Integrative Brain Research, Seattle Children’s Research Institute, University of Washington, Seattle, WA 98101, USADepartment of Psychiatry, Neuroscience Program and Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158, USADepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143-0628, USADepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USAQueensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, AustraliaThe corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.http://www.sciencedirect.com/science/article/pii/S2211124716312554astrocytecallosal agenesisinterhemispheric fissureFgf8NfiaNfib |
spellingShingle | Ilan Gobius Laura Morcom Rodrigo Suárez Jens Bunt Polina Bukshpun William Reardon William B. Dobyns John L.R. Rubenstein A. James Barkovich Elliott H. Sherr Linda J. Richards Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum Cell Reports astrocyte callosal agenesis interhemispheric fissure Fgf8 Nfia Nfib |
title | Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum |
title_full | Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum |
title_fullStr | Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum |
title_full_unstemmed | Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum |
title_short | Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum |
title_sort | astroglial mediated remodeling of the interhemispheric midline is required for the formation of the corpus callosum |
topic | astrocyte callosal agenesis interhemispheric fissure Fgf8 Nfia Nfib |
url | http://www.sciencedirect.com/science/article/pii/S2211124716312554 |
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