The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis

Kerloch, T.; Farrugia, F.; Maitre, M.; Terral, G.; Koehl, M.; Heng, J. I.-T.; Blanchard, M.; Doat, H.; Leste-Lasserre, T.; Goron, A.; Gonzales, D.; Guillemot, F.; Abrous, N.; Pacary, E.

doi:10.1101/2020.09.10.290866

bioRxiv · 10.1101/2020.09.10.290866

The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis

Kerloch, T.·Farrugia, F.·Maitre, M.·Terral, G.·Koehl, M.·Heng, J. I.-T.·Blanchard, M.·Doat, H.·Leste-Lasserre, T.·Goron, A.·Gonzales, D.·Guillemot, F.·Abrous, N.·Pacary, E.

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Abstract

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 the 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 behaviour whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results provide mechanistic insight into the differential regulation of hippocampal neurogenesis during development and adulthood, and establishes a causal relationship between Rnd2 expression and anxiety.

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Kerloch, T., Farrugia, F., Maitre, M., Terral, G., Koehl, M., Heng, J. I.-T., Blanchard, M., Doat, H., Leste-Lasserre, T., Goron, A., Gonzales, D., Guillemot, F., Abrous, N., Pacary, E.. 2020-09-10. The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis. https://doi.org/10.1101/2020.09.10.290866

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