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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2016-10-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716312554
_version_ 1818336493165346816
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
work_keys_str_mv AT ilangobius astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT lauramorcom astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT rodrigosuarez astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT jensbunt astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT polinabukshpun astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT williamreardon astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT williambdobyns astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT johnlrrubenstein astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT ajamesbarkovich astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT elliotthsherr astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum
AT lindajrichards astroglialmediatedremodelingoftheinterhemisphericmidlineisrequiredfortheformationofthecorpuscallosum