Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit
Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:8c131fd67c234cbf982e2d29b237469b2021-11-17T14:38:08ZMegalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit10.7554/eLife.713792050-084Xe71379https://doaj.org/article/8c131fd67c234cbf982e2d29b237469b2021-11-01T00:00:00Zhttps://elifesciences.org/articles/71379https://doaj.org/toc/2050-084XAbsence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes. Perivascular astrocytic processes along with blood vessels form the gliovascular unit. It was not previously known how MLC1 influences the physiology of the gliovascular unit. Here, using the Mlc1 knock-out mouse model of MLC, we demonstrated that MLC1 controls the postnatal development and organization of perivascular astrocytic processes, vascular smooth muscle cell contractility, neurovascular coupling, and intraparenchymal interstitial fluid clearance. Our data suggest that MLC is a developmental disorder of the gliovascular unit, and perivascular astrocytic processes and vascular smooth muscle cell maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.Alice GilbertXabier Elorza-VidalArmelle RancillacAudrey ChagnotMervé YetimVincent HingotThomas DeffieuxAnne-Cécile BoulayRodrigo Alvear-PerezSalvatore CisterninoSabrina MartinSonia TaïbAontoinette GelotVirginie MignonMaryline FavierIsabelle BrunetXavier DeclèvesMickael TanterRaul EstevezDenis VivienBruno SaubaméaMartine Cohen-SalmoneLife Sciences Publications LtdarticleMLCMLC1gliovascular unitastrocytesdevelopmentMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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MLC MLC1 gliovascular unit astrocytes development Medicine R Science Q Biology (General) QH301-705.5 |
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MLC MLC1 gliovascular unit astrocytes development Medicine R Science Q Biology (General) QH301-705.5 Alice Gilbert Xabier Elorza-Vidal Armelle Rancillac Audrey Chagnot Mervé Yetim Vincent Hingot Thomas Deffieux Anne-Cécile Boulay Rodrigo Alvear-Perez Salvatore Cisternino Sabrina Martin Sonia Taïb Aontoinette Gelot Virginie Mignon Maryline Favier Isabelle Brunet Xavier Declèves Mickael Tanter Raul Estevez Denis Vivien Bruno Saubaméa Martine Cohen-Salmon Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| description |
Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes. Perivascular astrocytic processes along with blood vessels form the gliovascular unit. It was not previously known how MLC1 influences the physiology of the gliovascular unit. Here, using the Mlc1 knock-out mouse model of MLC, we demonstrated that MLC1 controls the postnatal development and organization of perivascular astrocytic processes, vascular smooth muscle cell contractility, neurovascular coupling, and intraparenchymal interstitial fluid clearance. Our data suggest that MLC is a developmental disorder of the gliovascular unit, and perivascular astrocytic processes and vascular smooth muscle cell maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease. |
| format |
article |
| author |
Alice Gilbert Xabier Elorza-Vidal Armelle Rancillac Audrey Chagnot Mervé Yetim Vincent Hingot Thomas Deffieux Anne-Cécile Boulay Rodrigo Alvear-Perez Salvatore Cisternino Sabrina Martin Sonia Taïb Aontoinette Gelot Virginie Mignon Maryline Favier Isabelle Brunet Xavier Declèves Mickael Tanter Raul Estevez Denis Vivien Bruno Saubaméa Martine Cohen-Salmon |
| author_facet |
Alice Gilbert Xabier Elorza-Vidal Armelle Rancillac Audrey Chagnot Mervé Yetim Vincent Hingot Thomas Deffieux Anne-Cécile Boulay Rodrigo Alvear-Perez Salvatore Cisternino Sabrina Martin Sonia Taïb Aontoinette Gelot Virginie Mignon Maryline Favier Isabelle Brunet Xavier Declèves Mickael Tanter Raul Estevez Denis Vivien Bruno Saubaméa Martine Cohen-Salmon |
| author_sort |
Alice Gilbert |
| title |
Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| title_short |
Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| title_full |
Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| title_fullStr |
Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| title_full_unstemmed |
Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| title_sort |
megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/8c131fd67c234cbf982e2d29b237469b |
| work_keys_str_mv |
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| _version_ |
1718425428301971456 |