article published yes Xuying Zhang author Christine V. Mennicke author Guanxi Xiao author Robert J Beattie author 2E26DF60-F248-11E8-B48F-1D18A9856A870000-0002-8483-8753 Mansoor Haider author Simon Hippenmeyer author 37B36620-F248-11E8-B48F-1D18A9856A870000-0003-2279-1061 H. Troy Ghashghaei author SiHi department Molecular Mechanisms Regulating Gliogenesis in the Neocortex project Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development project <jats:p>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.</jats:p> https://research-explorer.ista.ac.at/download/8949/8950/2020_Cells_Zhang.pdf application/pdfno MDPI2020 eng 2073-4409 33322301 00060178730000110.3390/cells9122662 912 X. Zhang <i>et al.</i>, “Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,” <i>Cells</i>, vol. 9, no. 12. MDPI, 2020. 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. <i>Cells</i>. 2020;9(12). doi:<a href="https://doi.org/10.3390/cells9122662">10.3390/cells9122662</a> Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer, S., &#38; Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage. <i>Cells</i>. MDPI. <a href="https://doi.org/10.3390/cells9122662">https://doi.org/10.3390/cells9122662</a> Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.” <i>Cells</i>, vol. 9, no. 12, 2662, MDPI, 2020, doi:<a href="https://doi.org/10.3390/cells9122662">10.3390/cells9122662</a>. 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.” <i>Cells</i>. MDPI, 2020. <a href="https://doi.org/10.3390/cells9122662">https://doi.org/10.3390/cells9122662</a>. 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. X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer, H.T. Ghashghaei, Cells 9 (2020). 89492020-12-14T08:04:03Z2025-06-12T07:02:43Z