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Urokinase Receptor uPAR Overexpression in Mouse Brain Stimulates the Migration of Neurons into the Cortex during Embryogenesis

  • MOLECULAR DEVELOPMENTAL BIOLOGY
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Abstract

The regulation of neuronal migration in the cerebral cortex during embryonic development is one of the most important but underinvestigated processes that determines the correct formation of neural networks and the development of cognitive functions. Mutations of the urokinase receptor (uPAR) gene in mice lead to spontaneous seizures; polymorphisms of the PLAUR gene encoding uPAR in humans are associated with autism spectrum disorders. The effect of uPAR overexpression on the radial migration of neurons in the cerebral cortex during mouse embryogenesis has been investigated. The number of neurons migrating from the ventricular zone of proliferating progenitors to the outer layers of the cerebral cortex was evaluated. We found that uPAR overexpression significantly stimulates radial neuronal migration to the outer layers of the differentiating cortex. These data show for the first time uPAR-dependent regulation of neuronal migration in the embryonic period of the cerebral cortex development. Further study of uPAR’s role in regulating the migration trajectory of neuronal precursors will advance our understanding of the mechanisms of brain formation in health and disease.

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Funding

The reported study was funded by RFBR, project number 20-015-00186.

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Authors and Affiliations

  1. Laboratory of Molecular Endocrinology, Federal State Budgetary Organization National Cardiology Research Center of the Ministry of Health of the Russian Federation, Institute of Experimental Cardiology, 121552, Moscow, Russia

    A. A. Shmakova, A. V. Balatskiy, K. D. Rysenkova, V. A. Tkachuk & E. V. Semina

  2. Laboratory of Gene and Cell Technologies, Faculty of Medicine, Moscow State University, 119991, Moscow, Russia

    M. A. Kulebyakina, M. N. Karagyaur, K. Yu. Kulebyakin, K. D. Rysenkova, V. A. Tkachuk & E. V. Semina

  3. Institute of Cell Biology and Neurobiology of Charité, Universitätsmedizin Berlin, 10117, Berlin, Germany

    T. Schaub & V. S. Tarabykin

  4. Department of Laboratory Diagnostics, Medical Scientific and Educational Center of Moscow State University, 119192, Moscow, Russia

    A. V. Balatskiy

  5. Brain Development Genetics Laboratory, Institute of Neuroscience, Lobachevsky State University of Nizhni Novgorod, 603950, Nizhny Novgorod, Russia

    V. S. Tarabykin

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  1. A. A. Shmakova
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  2. A. V. Balatskiy
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  3. M. A. Kulebyakina
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  5. M. N. Karagyaur
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  6. K. Yu. Kulebyakin
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  7. K. D. Rysenkova
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  8. V. S. Tarabykin
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  9. V. A. Tkachuk
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  10. E. V. Semina
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Contributions

V.S. Tarabykin and E.V. Semina came up with and developed the experiment. A.V. Balatsky, M.A. Kulebyakina, T. Schaub, E.V. Semina, M.N. Karagyaur, K.Yu. Kulebyakin, and K.D. Rysenkova conducted the experiments. A.A. Shmakova compiled the algorithm and processed the data. A.A. Shmakova and E.V. Semina participated in the preparation and writing of the manuscript. A.V. Balatsky, M.A. Kulebyakina, and V.S. Tarabykin participated in editing the text. V.A. Tkachuk and E.V. Semina made significant contributions to the concept of the manuscript. All authors participated in the discussion of the results.

Corresponding author

Correspondence to E. V. Semina.

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Conflict of interest. The authors declare that they have no conflict of interests.

Statement on the welfare of animals. When performing this study, all manipulations carried out with experimental animals, methods of anesthesia, euthanasia, and animal care before and after experimental interventions were in accordance with international bioethics standards. No people were used as research subjects in this study.

ADDITIONAL MATERIALS

The program code in the R language for image analysis used in the work is available at the link https://osf.io/ahcg4/ ?view_only=b6281fbf091c48f1ae96c743f5d5d26a (https:// doi.org/10.17605/OSF.IO/AHCG4).

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Shmakova, A.A., Balatskiy, A.V., Kulebyakina, M.A. et al. Urokinase Receptor uPAR Overexpression in Mouse Brain Stimulates the Migration of Neurons into the Cortex during Embryogenesis. Russ J Dev Biol 52, 53–63 (2021). https://doi.org/10.1134/S1062360421010069

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  • DOI: https://doi.org/10.1134/S1062360421010069

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