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 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.

Abstract:
In nonhuman mammals and in particular in rodents, most granule neurons of the dentate gyrus (DG) are generated during development and yet little is known about their properties compared with adult-born neurons. Although it is generally admitted that these populations are morphologically indistinguishable once mature, a detailed analysis of developmentally born neurons is lacking. Here, we used in vivo electroporation to label dentate granule cells (DGCs) generated in mouse embryos (E14.5) or in neonates (P0) and followed their morphological development up to 6 months after birth. By comparison with mature retrovirus-labeled DGCs born at weaning (P21) or young adult (P84) stages, we provide the evidence that perinatally born neurons, especially embryonically born cells, are morphologically distinct from later-born neurons and are thus easily distinguishable. In addition, our data indicate that semilunar and hilar GCs, 2 populations in ectopic location, are generated during the embryonic and the neonatal periods, respectively. Thus, our findings provide new insights into the development of the different populations of GCs in the DG and open new questions regarding their function in the brain.

Abstract:
The cerebral cortex is the site of higher human cognitive and motor functions. Histologically, it is organized into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection neurons and inhibitory interneurons. The stereotyped cellular distribution of cortical neurons is crucial for the formation of functional neural circuits and it is predominantly established during embryonic development. Cortical neuron development is a multiphasic process characterized by sequential steps of neural progenitor proliferation, cell cycle exit, neuroblast migration and neuronal differentiation. This series of events requires an extensive and dynamic remodeling of the cell cytoskeleton at each step of the process. As major regulators of the cytoskeleton, the family of small Rho GTPases has been shown to play essential functions in cerebral cortex development. Here we review in vivo findings that support the contribution of Rho GTPases to cortical projection neuron development and we address their involvement in the etiology of cerebral cortex malformations.