TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway
TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in the modulation of important cellular pathways and master regulators of transcriptional output, including nuclear receptor repressors, Wnt signaling, and MECP2...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-02-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.641410/full |
| _version_ | 1818877405384671232 |
|---|---|
| author | Giuseppina Mastrototaro Mattia Zaghi Luca Massimino Matteo Moneta Neda Mohammadi Federica Banfi Edoardo Bellini Marzia Indrigo Giulia Fagnocchi Anna Bagliani Stefano Taverna Maria Rohm Maria Rohm Maria Rohm Maria Rohm Stephan Herzig Stephan Herzig Stephan Herzig Stephan Herzig Alessandro Sessa |
| author_facet | Giuseppina Mastrototaro Mattia Zaghi Luca Massimino Matteo Moneta Neda Mohammadi Federica Banfi Edoardo Bellini Marzia Indrigo Giulia Fagnocchi Anna Bagliani Stefano Taverna Maria Rohm Maria Rohm Maria Rohm Maria Rohm Stephan Herzig Stephan Herzig Stephan Herzig Stephan Herzig Alessandro Sessa |
| author_sort | Giuseppina Mastrototaro |
| collection | DOAJ |
| description | TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in the modulation of important cellular pathways and master regulators of transcriptional output, including nuclear receptor repressors, Wnt signaling, and MECP2 protein. However, TBL1XR1 mutations (including complete loss of its functions) have not been experimentally studied in a neurological context, leaving a knowledge gap in the mechanisms at the basis of the diseases. Here, we show that Tbl1xr1 knock-out mice exhibit behavioral and neuronal abnormalities. Either the absence of TBL1XR1 or its point mutations interfering with stability/regulation of NCOR complex induced decreased proliferation and increased differentiation in neural progenitors. We suggest that this developmental unbalance is due to a failure in the regulation of the MAPK cascade. Taken together, our results broaden the molecular and functional aftermath of TBL1XR1 deficiency associated with human disorders. |
| first_indexed | 2024-12-19T13:57:46Z |
| format | Article |
| id | doaj.art-076eed598f6b43d8bc228831b23603d0 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-19T13:57:46Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-076eed598f6b43d8bc228831b23603d02022-12-21T20:18:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.641410641410TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK PathwayGiuseppina Mastrototaro0Mattia Zaghi1Luca Massimino2Matteo Moneta3Neda Mohammadi4Federica Banfi5Edoardo Bellini6Marzia Indrigo7Giulia Fagnocchi8Anna Bagliani9Stefano Taverna10Maria Rohm11Maria Rohm12Maria Rohm13Maria Rohm14Stephan Herzig15Stephan Herzig16Stephan Herzig17Stephan Herzig18Alessandro Sessa19Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyNeurimmunology Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyMedical Oncology Unit, ASST Ovest Milanese, Legnano Hospital, Legnano, ItalyNeurimmunology Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyInstitute for Diabetes and Cancer IDC, Helmholtz Center, Munich, GermanyJoint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, GermanyMedical Faculty, Technical University Munich, Munich, GermanyGerman Center for Diabetes Research, Oberschleissheim, GermanyInstitute for Diabetes and Cancer IDC, Helmholtz Center, Munich, GermanyJoint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, GermanyMedical Faculty, Technical University Munich, Munich, GermanyGerman Center for Diabetes Research, Oberschleissheim, GermanyStem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, ItalyTBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in the modulation of important cellular pathways and master regulators of transcriptional output, including nuclear receptor repressors, Wnt signaling, and MECP2 protein. However, TBL1XR1 mutations (including complete loss of its functions) have not been experimentally studied in a neurological context, leaving a knowledge gap in the mechanisms at the basis of the diseases. Here, we show that Tbl1xr1 knock-out mice exhibit behavioral and neuronal abnormalities. Either the absence of TBL1XR1 or its point mutations interfering with stability/regulation of NCOR complex induced decreased proliferation and increased differentiation in neural progenitors. We suggest that this developmental unbalance is due to a failure in the regulation of the MAPK cascade. Taken together, our results broaden the molecular and functional aftermath of TBL1XR1 deficiency associated with human disorders.https://www.frontiersin.org/articles/10.3389/fcell.2021.641410/fullTBL1XR1NCORbrain developmentneurodevelopmental disordersMAPK |
| spellingShingle | Giuseppina Mastrototaro Mattia Zaghi Luca Massimino Matteo Moneta Neda Mohammadi Federica Banfi Edoardo Bellini Marzia Indrigo Giulia Fagnocchi Anna Bagliani Stefano Taverna Maria Rohm Maria Rohm Maria Rohm Maria Rohm Stephan Herzig Stephan Herzig Stephan Herzig Stephan Herzig Alessandro Sessa TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway Frontiers in Cell and Developmental Biology TBL1XR1 NCOR brain development neurodevelopmental disorders MAPK |
| title | TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway |
| title_full | TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway |
| title_fullStr | TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway |
| title_full_unstemmed | TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway |
| title_short | TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway |
| title_sort | tbl1xr1 ensures balanced neural development through ncor complex mediated regulation of the mapk pathway |
| topic | TBL1XR1 NCOR brain development neurodevelopmental disorders MAPK |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.641410/full |
| work_keys_str_mv | AT giuseppinamastrototaro tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT mattiazaghi tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT lucamassimino tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT matteomoneta tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT nedamohammadi tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT federicabanfi tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT edoardobellini tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT marziaindrigo tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT giuliafagnocchi tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT annabagliani tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT stefanotaverna tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT mariarohm tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT mariarohm tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT mariarohm tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT mariarohm tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT stephanherzig tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT stephanherzig tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT stephanherzig tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT stephanherzig tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway AT alessandrosessa tbl1xr1ensuresbalancedneuraldevelopmentthroughncorcomplexmediatedregulationofthemapkpathway |