An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold.
The mature mammalian cortex is composed of 6 architecturally and functionally distinct layers. Two key steps in the assembly of this layered structure are the initial establishment of the glial scaffold and the subsequent migration of postmitotic neurons to their final position. These processes invo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-08-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002212&type=printable |
| _version_ | 1797641144876662784 |
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| author | Wenny Wong Jason A Estep Alyssa M Treptow Niloofar Rajabli Jennifer N Jahncke Teresa Ubina Kevin M Wright Martin M Riccomagno |
| author_facet | Wenny Wong Jason A Estep Alyssa M Treptow Niloofar Rajabli Jennifer N Jahncke Teresa Ubina Kevin M Wright Martin M Riccomagno |
| author_sort | Wenny Wong |
| collection | DOAJ |
| description | The mature mammalian cortex is composed of 6 architecturally and functionally distinct layers. Two key steps in the assembly of this layered structure are the initial establishment of the glial scaffold and the subsequent migration of postmitotic neurons to their final position. These processes involve the precise and timely regulation of adhesion and detachment of neural cells from their substrates. Although much is known about the roles of adhesive substrates during neuronal migration and the formation of the glial scaffold, less is understood about how these signals are interpreted and integrated within these neural cells. Here, we provide in vivo evidence that Cas proteins, a family of cytoplasmic adaptors, serve a functional and redundant role during cortical lamination. Cas triple conditional knock-out (Cas TcKO) mice display severe cortical phenotypes that feature cobblestone malformations. Molecular epistasis and genetic experiments suggest that Cas proteins act downstream of transmembrane Dystroglycan and β1-Integrin in a radial glial cell-autonomous manner. Overall, these data establish a new and essential role for Cas adaptor proteins during the formation of cortical circuits and reveal a signaling axis controlling cortical scaffold formation. |
| first_indexed | 2024-03-11T13:41:21Z |
| format | Article |
| id | doaj.art-67998e8f6a124108821ba7ec1cb7b26e |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-03-11T13:41:21Z |
| publishDate | 2023-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-67998e8f6a124108821ba7ec1cb7b26e2023-11-02T11:47:57ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-08-01218e300221210.1371/journal.pbio.3002212An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold.Wenny WongJason A EstepAlyssa M TreptowNiloofar RajabliJennifer N JahnckeTeresa UbinaKevin M WrightMartin M RiccomagnoThe mature mammalian cortex is composed of 6 architecturally and functionally distinct layers. Two key steps in the assembly of this layered structure are the initial establishment of the glial scaffold and the subsequent migration of postmitotic neurons to their final position. These processes involve the precise and timely regulation of adhesion and detachment of neural cells from their substrates. Although much is known about the roles of adhesive substrates during neuronal migration and the formation of the glial scaffold, less is understood about how these signals are interpreted and integrated within these neural cells. Here, we provide in vivo evidence that Cas proteins, a family of cytoplasmic adaptors, serve a functional and redundant role during cortical lamination. Cas triple conditional knock-out (Cas TcKO) mice display severe cortical phenotypes that feature cobblestone malformations. Molecular epistasis and genetic experiments suggest that Cas proteins act downstream of transmembrane Dystroglycan and β1-Integrin in a radial glial cell-autonomous manner. Overall, these data establish a new and essential role for Cas adaptor proteins during the formation of cortical circuits and reveal a signaling axis controlling cortical scaffold formation.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002212&type=printable |
| spellingShingle | Wenny Wong Jason A Estep Alyssa M Treptow Niloofar Rajabli Jennifer N Jahncke Teresa Ubina Kevin M Wright Martin M Riccomagno An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. PLoS Biology |
| title | An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. |
| title_full | An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. |
| title_fullStr | An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. |
| title_full_unstemmed | An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. |
| title_short | An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. |
| title_sort | adhesion signaling axis involving dystroglycan β1 integrin and cas adaptor proteins regulates the establishment of the cortical glial scaffold |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002212&type=printable |
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