RT Journal Article
SR Electronic
T1 Non-cell autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 710848
DO 10.1101/710848
A1 C. Vincent
A1 J. Gilabert-Juan
A1 R. Gibel-Russo
A1 D. Alvarez-Fischer
A1 M.-O. Krebs
A1 G. Le Pen
A1 A. Prochiantz
A1 A.A. Di Nardo
YR 2021
UL http://biorxiv.org/content/early/2021/01/05/710848.abstract
AB The Otx2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, a mesencephalic nucleus involved in the control of complex behaviors through its projections to limbic structures, including the ventral hippocampus, amygdala, nucleus accumbens and medial prefrontal cortex. We find adult mice heterozygous for Otx2 show anxiolysis-like phenotype in light-dark box and elevated plus maze paradigms. However, the number of dopaminergic neurons, the integrity of their axons, their projection patterns in target structures, and the amounts of dopamine and dopamine metabolites in targets structures were not modified. Because OTX2 is expressed by the choroid plexus, secreted into cerebrospinal fluid and transferred to parvalbumin interneurons of the cortex, hippocampus, and amygdala, we investigated if this phenotype could result from the decreased synthesis of OTX2 in the choroid plexus. Indeed, the anxiolysis-like phenotype was partially recapitulated in the Otx2+/AA and scFvOtx2tg/0 choroid-plexus dependent non-cell-autonomous OTX2 loss of function mouse models. Furthermore, the phenotype was reversed by the overexpression of Otx2 specifically in choroid plexus of adult Otx2 heterozygous mice. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of the anxiety phenotype in the mouse.Competing Interest StatementThe authors have declared no competing interest.