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Zinc Uptake and Storage During the Formation of the Cerebral Cortex in Mice

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Abstract

The cerebral cortex (or neocortex) is a brain structure formed during embryogenesis. The present study seeks to provide a detailed characterization of the Zn homeostatic mechanisms during cerebral cortex formation and development. To reach that goal, we have combined high-throughput RNA-sequencing analysis of the whole murine genome, X-ray fluorescence nanoimaging (XRF), inductively coupled plasma-atomic emission spectrometry (ICP-AES), and live-cell imaging of dissociated cortical neurons loaded with the Zn fluorescent probe FluoZin-3. The transcriptomic analysis was conducted from mRNAs isolated from cortices collected at embryonic (E) days 11 (E11), E13, and E17 and on postnatal day 1 (PN1) pups. This permitted to characterize the temporal pattern of expression of the main genes participating in the cellular transport, storage, and release of Zn during corticogenesis. It appears that cells of the immature cortex express a wide diversity of actors involved in Zn homeostasis with Zip7, SOD1, and metallothioneins being the most abundant transcripts throughout corticogenesis. The quantification of total Zn with XRF and ICP-AES reveals a reduction of Zn levels. Moreover, this is accompanied by a diminution of the size of the internal pools of mobilizable Zn. This study illustrates the tight temporal and spatial regulation of Zn homeostasis during cerebral brain development.

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Acknowledgements

We wish to thank Dr. J. Pérard for his assistance with the ICP-AES experiments and L. Macari for her help with the cell cultures.

Funding

The study was supported by a grant from l’Agence Nationale de la Recherche (ANR-16-CE29-0024 to AB). We also wish to acknowledge the support from the Centre National de la Recherche Scientifique (CNRS), the Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), the Université de Grenoble Alpes (UGA), and the France Génomique infrastructure, funded as part of the “Investissements d’Avenir” program managed by the Agence Nationale de la Recherche (contract ANR-10-INBS-09).

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Authors and Affiliations

  1. Université Grenoble Alpes, CNRS, CEA, BIG-LCBM, 38000, Grenoble, France

    Jessy Hasna & Alexandre Bouron

  2. ESRF, Grenoble, France

    Sylvain Bohic

  3. Institut de biologie de l’Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005, Paris, France

    Sophie Lemoine & Corinne Blugeon

  4. Laboratoire de Chimie et Biologie des Métaux, UMR CNRS 5249, CEA, 17 rue des Martyrs, 38054, Grenoble, France

    Alexandre Bouron

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  1. Jessy Hasna
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Correspondence to Alexandre Bouron.

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The experimental protocol was approved by the ethical committee of the CEA’s Life Sciences Division (CETEA, # A14-006).

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Hasna, J., Bohic, S., Lemoine, S. et al. Zinc Uptake and Storage During the Formation of the Cerebral Cortex in Mice. Mol Neurobiol 56, 6928–6940 (2019). https://doi.org/10.1007/s12035-019-1581-7

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