--- _id: '8949' abstract: - lang: eng text: Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis. acknowledgement: This research was funded by grants from the National Institutes of Health to H.T.G. (R01NS098370 and R01NS089795). C.V.M. was supported by a National Science Foundation Graduate Research Fellowship (DGE-1746939). R.B. was supported by the FWF Lise-Meitner program (M 2416), and S.H. was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 725780 LinPro).The authors thank members of the Ghashghaei lab for discussions, technical support, and help with preparation of the manuscript. article_number: '2662' article_processing_charge: No article_type: original author: - first_name: Xuying full_name: Zhang, Xuying last_name: Zhang - first_name: Christine V. full_name: Mennicke, Christine V. last_name: Mennicke - first_name: Guanxi full_name: Xiao, Guanxi last_name: Xiao - 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: Mansoor full_name: Haider, Mansoor last_name: Haider - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: H. Troy full_name: Ghashghaei, H. Troy last_name: Ghashghaei citation: ama: Zhang X, Mennicke CV, Xiao G, et al. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. 2020;9(12). doi:10.3390/cells9122662 apa: Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer, S., & Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. MDPI. https://doi.org/10.3390/cells9122662 chicago: Zhang, Xuying, Christine V. Mennicke, Guanxi Xiao, Robert J Beattie, Mansoor Haider, Simon Hippenmeyer, and H. Troy Ghashghaei. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” Cells. MDPI, 2020. https://doi.org/10.3390/cells9122662. ieee: X. Zhang et al., “Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,” Cells, vol. 9, no. 12. MDPI, 2020. ista: Zhang X, Mennicke CV, Xiao G, Beattie RJ, Haider M, Hippenmeyer S, Ghashghaei HT. 2020. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. Cells. 9(12), 2662. mla: Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” Cells, vol. 9, no. 12, 2662, MDPI, 2020, doi:10.3390/cells9122662. short: X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer, H.T. Ghashghaei, Cells 9 (2020). date_created: 2020-12-14T08:04:03Z date_published: 2020-12-11T00:00:00Z date_updated: 2023-08-24T10:57:48Z day: '11' ddc: - '570' department: - _id: SiHi doi: 10.3390/cells9122662 ec_funded: 1 external_id: isi: - '000601787300001' file: - access_level: open_access checksum: 5095cbdc728c9a510c5761cf60a8861c content_type: application/pdf creator: dernst date_created: 2020-12-14T08:09:43Z date_updated: 2020-12-14T08:09:43Z file_id: '8950' file_name: 2020_Cells_Zhang.pdf file_size: 3504525 relation: main_file success: 1 file_date_updated: 2020-12-14T08:09:43Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version project: - _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 publication: Cells publication_identifier: issn: - 2073-4409 publication_status: published publisher: MDPI quality_controlled: '1' status: public title: Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage 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: 9 year: '2020' ... --- _id: '8813' abstract: - lang: eng text: 'In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation.' article_processing_charge: No author: - first_name: Laura full_name: Santini, Laura last_name: Santini - first_name: Florian full_name: Halbritter, Florian last_name: Halbritter - first_name: Fabian full_name: Titz-Teixeira, Fabian last_name: Titz-Teixeira - first_name: Toru full_name: Suzuki, Toru last_name: Suzuki - first_name: Maki full_name: Asami, Maki last_name: Asami - first_name: Julia full_name: Ramesmayer, Julia last_name: Ramesmayer - first_name: Xiaoyan full_name: Ma, Xiaoyan last_name: Ma - first_name: Andreas full_name: Lackner, Andreas last_name: Lackner - first_name: Nick full_name: Warr, Nick last_name: Warr - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Ernest full_name: Laue, Ernest last_name: Laue - first_name: Matthias full_name: Farlik, Matthias last_name: Farlik - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Andreas full_name: Beyer, Andreas last_name: Beyer - first_name: Anthony C. F. full_name: Perry, Anthony C. F. last_name: Perry - first_name: Martin full_name: Leeb, Martin last_name: Leeb citation: ama: Santini L, Halbritter F, Titz-Teixeira F, et al. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv. doi:10.1101/2020.11.03.366948 apa: Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ramesmayer, J., … Leeb, M. (n.d.). Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.11.03.366948 chicago: Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Julia Ramesmayer, Xiaoyan Ma, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.11.03.366948. ieee: L. Santini et al., “Novel imprints in mouse blastocysts are predominantly DNA methylation independent,” bioRxiv. Cold Spring Harbor Laboratory. ista: Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ramesmayer J, Ma X, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer A, Perry ACF, Leeb M. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. bioRxiv, 10.1101/2020.11.03.366948. mla: Santini, Laura, et al. “Novel Imprints in Mouse Blastocysts Are Predominantly DNA Methylation Independent.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.11.03.366948. short: L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, J. Ramesmayer, X. Ma, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik, C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, BioRxiv (n.d.). date_created: 2020-11-26T07:17:19Z date_published: 2020-11-05T00:00:00Z date_updated: 2023-09-12T11:05:28Z day: '05' department: - _id: SiHi doi: 10.1101/2020.11.03.366948 external_id: pmid: - 'PPR234457 ' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.11.03.366948 month: '11' oa: 1 oa_version: Preprint pmid: 1 publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory status: public title: Novel imprints in mouse blastocysts are predominantly DNA methylation independent type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8569' abstract: - lang: eng text: Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell–cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future. acknowledgement: AH was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA Grant Agreement No. 618444 to SH. article_number: '574382' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Hansen AH, Hippenmeyer S. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 2020;8(9). doi:10.3389/fcell.2020.574382 apa: Hansen, A. H., & Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. Frontiers. https://doi.org/10.3389/fcell.2020.574382 chicago: Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” Frontiers in Cell and Developmental Biology. Frontiers, 2020. https://doi.org/10.3389/fcell.2020.574382. ieee: A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex,” Frontiers in Cell and Developmental Biology, vol. 8, no. 9. Frontiers, 2020. ista: Hansen AH, Hippenmeyer S. 2020. Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental Biology. 8(9), 574382. mla: Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” Frontiers in Cell and Developmental Biology, vol. 8, no. 9, 574382, Frontiers, 2020, doi:10.3389/fcell.2020.574382. short: A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology 8 (2020). date_created: 2020-09-26T06:11:07Z date_published: 2020-09-25T00:00:00Z date_updated: 2024-03-27T23:30:40Z day: '25' ddc: - '570' department: - _id: SiHi doi: 10.3389/fcell.2020.574382 ec_funded: 1 external_id: isi: - '000577915900001' pmid: - '33102480' file: - access_level: open_access checksum: 01f731824194c94c81a5da360d997073 content_type: application/pdf creator: dernst date_created: 2020-09-28T13:11:17Z date_updated: 2020-09-28T13:11:17Z file_id: '8584' file_name: 2020_Frontiers_Hansen.pdf file_size: 5527139 relation: main_file success: 1 file_date_updated: 2020-09-28T13:11:17Z has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration - _id: 25D61E48-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618444' name: Molecular Mechanisms of Cerebral Cortex Development publication: Frontiers in Cell and Developmental Biology publication_identifier: issn: - 2296-634X publication_status: published publisher: Frontiers quality_controlled: '1' related_material: record: - id: '9962' relation: dissertation_contains status: public scopus_import: '1' status: public title: Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex 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: 8 year: '2020' ... --- _id: '7815' abstract: - lang: eng text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl article_number: e61147 article_processing_charge: No article_type: original author: - 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: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. 2020;(159). doi:10.3791/61147 apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen, A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147 chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147. ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM),” Journal of Visual Experiments, no. 159. MyJove Corporation, 2020. ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159), e61147. mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147. short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen, S. Hippenmeyer, Journal of Visual Experiments (2020). date_created: 2020-05-11T08:31:20Z date_published: 2020-05-08T00:00:00Z date_updated: 2024-03-27T23:30:41Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.3791/61147 ec_funded: 1 external_id: isi: - '000546406600043' file: - access_level: open_access checksum: 3154ea7f90b9fb45e084cd1c2770597d content_type: application/pdf creator: rbeattie date_created: 2020-05-11T08:28:38Z date_updated: 2020-07-14T12:48:03Z file_id: '7816' file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf file_size: 1352186 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' isi: 1 issue: '159' language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: Journal of Visual Experiments publication_identifier: issn: - 1940-087X publication_status: published publisher: MyJove Corporation quality_controlled: '1' related_material: record: - id: '7902' relation: part_of_dissertation status: public scopus_import: '1' status: public title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM) 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7902' abstract: - lang: eng text: "Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.\r\nIn summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.\r\nThis work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation." acknowledged_ssus: - _id: PreCl - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras citation: ama: Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902 apa: Contreras, X. (2020). Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7902 chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7902. ieee: X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020. ista: Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7902. short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020. date_created: 2020-05-29T08:27:32Z date_published: 2020-06-05T00:00:00Z date_updated: 2023-10-18T08:45:16Z day: '05' ddc: - '570' degree_awarded: PhD department: - _id: SiHi doi: 10.15479/AT:ISTA:7902 ec_funded: 1 file: - access_level: closed checksum: 43c172bf006c95b65992d473c7240d13 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: xcontreras date_created: 2020-06-05T08:18:08Z date_updated: 2021-06-07T22:30:03Z embargo_to: open_access file_id: '7927' file_name: PhDThesis_Contreras.docx file_size: 53134142 relation: source_file - access_level: open_access checksum: addfed9128271be05cae3608e03a6ec0 content_type: application/pdf creator: xcontreras date_created: 2020-06-05T08:18:07Z date_updated: 2021-06-07T22:30:03Z embargo: 2021-06-06 file_id: '7928' file_name: PhDThesis_Contreras.pdf file_size: 35117191 relation: main_file file_date_updated: 2021-06-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '214' project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6830' relation: dissertation_contains status: public - id: '28' relation: dissertation_contains status: public - id: '7815' relation: dissertation_contains status: public status: public supervisor: - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 title: Genetic dissection of neural development in health and disease at single cell resolution type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ...