Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization.
Radial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. RGCs have an elongated bipolar morphology with basal and apical endfeet that reside in distinct niches. Yet, how this subcellular compartmentalization of RGCs controls cortical development...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2023-02-01
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Series: | PLoS Biology |
Online Access: | https://doi.org/10.1371/journal.pbio.3001926 |
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author | Brooke R D'Arcy Ashley L Lennox Camila Manso Musso Annalise Bracher Carla Escobar-Tomlienovich Stephany Perez-Sanchez Debra L Silver |
author_facet | Brooke R D'Arcy Ashley L Lennox Camila Manso Musso Annalise Bracher Carla Escobar-Tomlienovich Stephany Perez-Sanchez Debra L Silver |
author_sort | Brooke R D'Arcy |
collection | DOAJ |
description | Radial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. RGCs have an elongated bipolar morphology with basal and apical endfeet that reside in distinct niches. Yet, how this subcellular compartmentalization of RGCs controls cortical development is largely unknown. Here, we employ in vivo proximity labeling, in the mouse, using unfused BirA to generate the first subcellular proteome of RGCs and uncover new principles governing local control of cortical development. We discover a cohort of proteins that are significantly enriched in RGC basal endfeet, with MYH9 and MYH10 among the most abundant. Myh9 and Myh10 transcripts also localize to endfeet with distinct temporal dynamics. Although they each encode isoforms of non-muscle myosin II heavy chain, Myh9 and Myh10 have drastically different requirements for RGC integrity. Myh9 loss from RGCs decreases branching complexity and causes endfoot protrusion through the basement membrane. In contrast, Myh10 controls endfoot adhesion, as mutants have unattached apical and basal endfeet. Finally, we show that Myh9- and Myh10-mediated regulation of RGC complexity and endfoot position non-cell autonomously controls interneuron number and organization in the marginal zone. Our study demonstrates the utility of in vivo proximity labeling for dissecting local control of complex systems and reveals new mechanisms for dictating RGC integrity and cortical architecture. |
first_indexed | 2024-03-12T23:37:51Z |
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institution | Directory Open Access Journal |
issn | 1544-9173 1545-7885 |
language | English |
last_indexed | 2024-03-12T23:37:51Z |
publishDate | 2023-02-01 |
publisher | Public Library of Science (PLoS) |
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spelling | doaj.art-8f39ed4bfa7a4fadbc662860843071fa2023-07-15T05:30:33ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-02-01212e300192610.1371/journal.pbio.3001926Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization.Brooke R D'ArcyAshley L LennoxCamila Manso MussoAnnalise BracherCarla Escobar-TomlienovichStephany Perez-SanchezDebra L SilverRadial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. RGCs have an elongated bipolar morphology with basal and apical endfeet that reside in distinct niches. Yet, how this subcellular compartmentalization of RGCs controls cortical development is largely unknown. Here, we employ in vivo proximity labeling, in the mouse, using unfused BirA to generate the first subcellular proteome of RGCs and uncover new principles governing local control of cortical development. We discover a cohort of proteins that are significantly enriched in RGC basal endfeet, with MYH9 and MYH10 among the most abundant. Myh9 and Myh10 transcripts also localize to endfeet with distinct temporal dynamics. Although they each encode isoforms of non-muscle myosin II heavy chain, Myh9 and Myh10 have drastically different requirements for RGC integrity. Myh9 loss from RGCs decreases branching complexity and causes endfoot protrusion through the basement membrane. In contrast, Myh10 controls endfoot adhesion, as mutants have unattached apical and basal endfeet. Finally, we show that Myh9- and Myh10-mediated regulation of RGC complexity and endfoot position non-cell autonomously controls interneuron number and organization in the marginal zone. Our study demonstrates the utility of in vivo proximity labeling for dissecting local control of complex systems and reveals new mechanisms for dictating RGC integrity and cortical architecture.https://doi.org/10.1371/journal.pbio.3001926 |
spellingShingle | Brooke R D'Arcy Ashley L Lennox Camila Manso Musso Annalise Bracher Carla Escobar-Tomlienovich Stephany Perez-Sanchez Debra L Silver Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization. PLoS Biology |
title | Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization. |
title_full | Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization. |
title_fullStr | Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization. |
title_full_unstemmed | Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization. |
title_short | Non-muscle myosins control radial glial basal endfeet to mediate interneuron organization. |
title_sort | non muscle myosins control radial glial basal endfeet to mediate interneuron organization |
url | https://doi.org/10.1371/journal.pbio.3001926 |
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