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OTX2 signals from the choroid plexus to regulate adult neurogenesis

Anabelle Planques, Vanessa Oliveira Moreira, Chantal Dubreuil, Alain Prochiantz, Ariel A Di Nardo
doi: https://doi.org/10.1101/243659
Anabelle Planques
1Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.
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Vanessa Oliveira Moreira
1Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.
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Chantal Dubreuil
1Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.
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Alain Prochiantz
1Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.
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Ariel A Di Nardo
1Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS UMR 7241, INSERM U1050, PSL Research University, Paris, France.
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Abstract

Proliferation and migration during adult neurogenesis are regulated by a microenvironment of signaling molecules originating from local vasculature, from cerebrospinal fluid produced by the choroid plexus, and from local supporting cells including astrocytes. Here, we focus on the function of OTX2 homeoprotein transcription factor in the mouse adult ventricular-subventricular zone (V-SVZ) which generates olfactory bulb neurons. We find that OTX2 secreted by choroid plexus is transferred to supporting cells of the V-SVZ and rostral migratory stream. Deletion of Otx2 in choroid plexus affects neuroblast migration and reduces the number of olfactory bulb newborn neurons. Adult neurogenesis was also decreased by expressing secreted single-chain antibodies to sequester OTX2 in the cerebrospinal fluid, demonstrating the importance of non-cell autonomous OTX2. We show that OTX2 activity modifies extracellular matrix components and signaling molecules produced by supporting astrocytes. Thus, we reveal a multi-level and non-cell autonomous role of a homeoprotein and reinforce the choroid plexus and astrocytes as key niche compartments affecting adult neurogenesis.

Significance Statement Cerebrospinal fluid, local vasculature and non-neurogenic astrocytes are niche compartments that provide a microenvironment for regulating adult mouse neurogenesis. We show that OTX2 homeoprotein secreted by choroid plexus into the cerebrospinal fluid is transferred into non-neurogenic astrocytes of the ventricular-subventricular zone and rostral migratory stream where it regulates extracellular matrix and signaling factors. This non-cell-autonomous activity impacts the number of newborn neurons that integrate the olfactory bulb. Thus, we reveal a multi-level role for OTX2 and reinforce the choroid plexus as a key niche compartment affecting adult neurogenesis.

Author Contributions

APl, VOM, APr and AAD designed the experiments; APl, VOM and CD performed the experiments; APl, VOM and AAD wrote the manuscript.

Footnotes

  • Funding sources: This work was supported by Région Ile-de-France via le DIM Cerveau et Pensée, by ERC Advanced Grant HOMEOSIGN n°339379, and by GRL Program n°2009-00424.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 08, 2019.
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OTX2 signals from the choroid plexus to regulate adult neurogenesis
Anabelle Planques, Vanessa Oliveira Moreira, Chantal Dubreuil, Alain Prochiantz, Ariel A Di Nardo
bioRxiv 243659; doi: https://doi.org/10.1101/243659
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OTX2 signals from the choroid plexus to regulate adult neurogenesis
Anabelle Planques, Vanessa Oliveira Moreira, Chantal Dubreuil, Alain Prochiantz, Ariel A Di Nardo
bioRxiv 243659; doi: https://doi.org/10.1101/243659

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