The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis
Mol Psy.. 2021-12; 26: 7280–7295
DOI: 10.1101/2020.09.10.290866
Kerloch T(1), Farrugia F(1), Bouit L(2), Maître M(3), Terral G(1), Koehl M(1), Mortessagne P(1), Heng JI(4), Blanchard M(1), Doat H(3)(5), Leste-Lasserre T(5), Goron A(1), Gonzales D(6), Perrais D(2), Guillemot F(7), Abrous DN(#)(1), Pacary E(#)(8).
Author information:
(1)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300, Bordeaux, France.
(2)Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000, Bordeaux, France.
(3)Laser microdissection Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300, Bordeaux, France.
(4)Curtin Health Innovation Research Institute, Curtin University, 6102, Bentley, WA, Australia.
(5)Transcriptome Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300, Bordeaux, France.
(6)Genotyping Facility, Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300, Bordeaux, France.
(7)The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
(8)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-3300, Bordeaux, France. .
(#)Contributed equally
Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion of Rnd2 in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression of Rnd2 in adult-born dentate granule neurons increases anxiety-like behavior whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results are in line with the view that adult neurogenesis is not a simple continuation of earlier processes from development, and establish a causal relationship between Rnd2 expression and anxiety.