Actin-based deformations of the nucleus control mouse multiciliated ependymal cell differentiation
Ependymal cells (ECs) are multiciliated cells in the brain that contribute to cerebrospinal fluid flow. ECs are specified during embryonic stages but differentiate later in development. Their differentiation depends on genes such as GEMC1 and MCIDAS in conjunction with E2F4/5 as well as on cell-cycle-related factors. In the mouse brain, we observe that nuclear deformation accompanies EC differentiation. Tampering with these deformations either by decreasing F-actin levels or by severing the link between the nucleus and the actin cytoskeleton blocks differentiation. Conversely, increasing F-actin by knocking out the Arp2/3 complex inhibitor Arpin or artificially deforming the nucleus activates differentiation. These data are consistent with actin polymerization triggering nuclear deformation and jump starting the signaling that produces ECs. A player in this process is the retinoblastoma 1 (RB1) protein, whose phosphorylation prompts MCIDAS activation. Overall, this study identifies a role for actin-based mechanical inputs to the nucleus as controlling factors in cell differentiation.
Authors
- Syed Kaabir Ali (ORCID: https://orcid.org/0000-0002-8111-2244)
- Alexia Bankolé (ORCID: https://orcid.org/0009-0008-9560-2077)
- Nathalie Delgehyr (ORCID: https://orcid.org/0000-0001-9870-0475)
- Alain Marty (ORCID: https://orcid.org/0000-0001-6478-6880)
- Ana‐Maria Lennon‐Duménil (ORCID: https://orcid.org/0000-0002-8220-4482)
- Nathalie Spassky (ORCID: https://orcid.org/0000-0003-4722-6464)
- Marion Faucourt
- Julie Plastino (ORCID: https://orcid.org/0000-0002-7808-5927)
- Ayako Yamada (ORCID: https://orcid.org/0000-0003-3162-3318)
- Alice Meunier (ORCID: https://orcid.org/0000-0001-6131-7747)
- Alexia Mahuzier
- Michella Khoury Damaa
- Ayush Srivastava (ORCID: https://orcid.org/0000-0003-1713-8893)
- Marianne Basso
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- École Normale Supérieure - PSL (FR)
- Sorbonne Université (FR)
- Institut Necker Enfants Malades (FR)
- Sorbonne Paris Cité (FR)
- École Normale Supérieure (BI)
- Institut de Biologie de l'École Normale Supérieure (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Developmental Cell
- Published
- 2024-12-10
- DOI
- https://doi.org/10.1016/j.devcel.2024.11.008
- Citations
- 4
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.30
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Fondation Pierre-Gilles de Gennes pour la recherche