OTX2 non-cell autonomous activity regulates anxiety-like behavior, by Ariel Di Nardo

Summary  OTX2 non-cell autonomous activity regulates anxiety-like behavior

Our laboratory has been working for several years on the role of non-cell autonomous homeoprotein transcription factors in regulating cerebral cortex physiology. We have shown that in mice the OTX2 homeoprotein is expressed in the choroid plexus, secreted into cerebrospinal fluid, and transferred into parvalbumin (PV)-expressing interneurons. OTX2 participates in PV cell maturation and regulates the timing of plasticity critical periods. These juvenile periods allow for remodeling of circuitry in response to the environmental and genetic contexts. They not only occur in primary sensory cortices but also in associative cortices such as the medial prefrontal cortex (mPFC). Consequently, they are associated with disease outcomes and support the neurodevelopmental hypothesis for some psychiatric disorders. Although our initial OTX2 studies were primarily focused on mouse visual system critical periods, we have have also investigated higher order circuits including mPFC. Indeed, other labs have recently reported causal links between OTX2 and anxiety-like behavior in rodents induced by early-life stress. I will detail what is known about OTX2 transfer in the postnatal brain regarding its target cells and genes, and will present recent findings showing that choroid plexus OTX2 affects adult mouse brain plasticity and animal behavior.

Short biography

Ariel Di Nardo co-directs a Labcom (CNRS – Inserm – Collège de France – BrainEver SAS) within the Center for Interdisciplinary Research in Biology at the Collège de France in Paris. He obtained his PhD studying protein folding at the University of Toronto, Canada, working with Prof. Alan Davidson. He carried out postdoctoral work with Prof. Alain Prochiantz at the Ecole Normale Supérieure Paris, studying neuronal homeoprotein transcription factor activity pertaining to the regulation of translation and dendritic localization. He helped discover homeoprotein involvement as a signaling factor in the postnatal development and physiology of the visual system. He joined the CNRS in 2008 with Prof. Alain Prochiantz in order to continue studying mechanisms of homeoprotein signaling. He has shown that homeoproteins in the cerebrospinal fluid regulate critical periods of neuronal circuit plasticity, impacting binocular vision, auditory maps, and anxiety-like behavior in the mouse. In addition to its fundamental aspects, his work has contributed to the field of transduction peptides and led to several biotechnological and biomedical developments.

Team’s web site