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A Gene Regulatory Model of Cortical Neurogenesis


Pfister, Sabina; Hauri, Andreas; Zubler, Frederic; Michel, Gabriela; Kennedy, Henry; DeHay, Colette; Douglas, Rodney (2018). A Gene Regulatory Model of Cortical Neurogenesis. bioRxiv 394734, bioRxiv.

Abstract

Sparse data describing mouse cortical neurogenesis were used to derive a model gene regulatory network (GRN) that is then able to control the quantitative cellular dynamics of the observed neurogenesis. Derivation of the network begins by estimating from the biological data a set of cell states and transition probabilities necessary to explain neurogenesis. We show that the stochastic transition between states can be implemented by the dynamics of a GRN comprising only 36 abstract genes. Finally, we demonstrate using detailed physical simulations of cell mitosis, and differentiation that this GRN is able to steer a population of neuroepithelial precursors through mitotic expansion and differentiation to form the quantitatively correct complex multicellular architectures of mouse cortical areas 3 and 6. We find that the same GRN is able to generate both areas though modulation of only one gene, suggesting that arealization of the cortical sheet may require only simple improvisations on a fundamental gene network. We conclude that even sparse phenotypic and cell lineage data can be used to infer fundamental properties of neurogenesis and its organization.

Abstract

Sparse data describing mouse cortical neurogenesis were used to derive a model gene regulatory network (GRN) that is then able to control the quantitative cellular dynamics of the observed neurogenesis. Derivation of the network begins by estimating from the biological data a set of cell states and transition probabilities necessary to explain neurogenesis. We show that the stochastic transition between states can be implemented by the dynamics of a GRN comprising only 36 abstract genes. Finally, we demonstrate using detailed physical simulations of cell mitosis, and differentiation that this GRN is able to steer a population of neuroepithelial precursors through mitotic expansion and differentiation to form the quantitatively correct complex multicellular architectures of mouse cortical areas 3 and 6. We find that the same GRN is able to generate both areas though modulation of only one gene, suggesting that arealization of the cortical sheet may require only simple improvisations on a fundamental gene network. We conclude that even sparse phenotypic and cell lineage data can be used to infer fundamental properties of neurogenesis and its organization.

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Additional indexing

Item Type:Working Paper
Communities & Collections:07 Faculty of Science > Institute of Neuroinformatics
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2018
Deposited On:05 Mar 2019 15:18
Last Modified:29 Jul 2020 10:20
Publisher:BioRxiv
Series Name:bioRxiv
ISSN:2164-7844
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/394734

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