--- _id: '7253' abstract: - lang: eng text: The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype. acknowledged_ssus: - _id: PreCl article_number: '195' article_processing_charge: No article_type: original author: - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter orcid: 0000-0002-7903-3010 - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Keiichi I. full_name: Nakayama, Keiichi I. last_name: Nakayama - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2 apa: Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., & Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-14077-2 chicago: Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2. ieee: S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer, “Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development,” Nature Communications, vol. 11. Springer Nature, 2020. ista: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 11, 195. mla: Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications, vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2. short: S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020). date_created: 2020-01-11T10:42:48Z date_published: 2020-01-10T00:00:00Z date_updated: 2023-08-17T14:23:41Z day: '10' ddc: - '570' department: - _id: SiHi doi: 10.1038/s41467-019-14077-2 ec_funded: 1 external_id: isi: - '000551459000005' file: - access_level: open_access checksum: ebf1ed522f4e0be8d94c939c1806a709 content_type: application/pdf creator: dernst date_created: 2020-01-13T07:42:31Z date_updated: 2020-07-14T12:47:54Z file_id: '7261' file_name: 2020_NatureComm_Laukoter.pdf file_size: 8063333 relation: main_file file_date_updated: 2020-07-14T12:47:54Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version project: - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development - _id: 25D92700-B435-11E9-9278-68D0E5697425 grant_number: LS13-002 name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/ scopus_import: '1' status: public title: Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2020' ...