Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage

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.

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Journal Article | Published | English
Author
Zhang, Xuying; Mennicke, Christine V.; Xiao, Guanxi; Beattie, Robert JIST Austria ; Haider, Mansoor; Hippenmeyer, SimonIST Austria ; Ghashghaei, H. Troy
Department
Abstract
<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>
Publishing Year
Date Published
2020-12-11
Journal Title
Cells
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.
Volume
9
Issue
12
Article Number
2662
ISSN
IST-REx-ID

Cite this

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
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
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.
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.
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.
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.
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