Genetic dissection of neural development in health and disease at single cell resolution

By: Contreras Paniagua, Ximena
Material type: TextTextPublisher: IST Austria 2020Online resources: Click here to access online
Contents:
Abstract
Acknowledgments
About the Author
List of Publications Appearing in Thesis
List of Figures
List of Tables
List of Symbols/Abbreviations
Chapter 1 - Introduction
Chapter 2 - A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis
Chapter 3 - Lineage Tracing and Clonal Analysis in the Developing Brain using Mosaic Analysis with Double Markers
Chapter 4 - Genetic Dissection of Neural Stem Cell Lineage Progression using Mosaic Analysis with Double Markers
Conclusion
References
Appendix - Key Reagents or Resources
Summary: 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. In 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. This work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation.
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Thesis

Abstract

Acknowledgments

About the Author

List of Publications Appearing in Thesis

List of Figures

List of Tables

List of Symbols/Abbreviations

Chapter 1 - Introduction

Chapter 2 - A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis

Chapter 3 - Lineage Tracing and Clonal Analysis in the Developing Brain using Mosaic Analysis with Double Markers

Chapter 4 - Genetic Dissection of Neural Stem Cell Lineage Progression using Mosaic Analysis with Double Markers

Conclusion

References

Appendix - Key Reagents or Resources

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. In 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. This work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation.

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