CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab

Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011
Otx2-glycosaminoglycan interactions for Otx2 transfer
in the visual cortex
Clémence Bernard, Julien Spatazza, Ariel Di Nardo and Alain Prochiantz
CNRS UMR 7233, Collège de France, Paris, France
Otx2 homeoprotein activates a critical period during which the visual cortex is
plastic. This signalling requires an activity-dependent intercellular transfer, as
Otx2 is not expressed in the visual cortex. We have shown that during postnatal
development, Otx2 is transferred specifically into parvalbumin (PV) GABAergic
interneurons and induces their maturation.
The specific internalization of Otx2 by PV-cells led us to study whether
glycosaminoglycans (GAG) present at the surface of PV cells, called perineuronal
nets (PNNs), are involved in Otx2 recognition. We find that PNN hydrolysis by a
chondroitinase, which reopens ocular dominance plasticity in adulthood, reduces
the number of Otx2-positive cells in the visual cortex. A consensus GAG-binding
motif containing an arginine-lysis (RK) doublet has been identified within Otx2
primary sequence. This motif has a high affinity for chondroitin sulfates,
antagonizes Otx2 specific internalization by PV cells in vivo, and reopens a
window of plasticity in the adult visual cortex. These results are not observed
when the RK doublet is replaced by 2 alanines.
We introduced this RK→AA mutation in a transgenic knock-in Otx2-AA mouse.
The preliminary immunohistochemical studies of these mice suggest that this
mutation disrupts the interaction between Otx2 and PNNs and impacts visual
circuits development. Indeed, in these mice, we observed dose-dependent changes
of PV and PNN staining intensity, which suggests a defect in PV interneuron
maturation. This will be confirmed by an electrophysiological study of these
Otx2-AA mice.
Presented by: Bernard, Clémence
93
Poster No 011
Green Session