Thesis defense – Thomas Kerloch

Etude du développement des neurones granulaires du gyrus denté: morphogénèse et régulation par Rnd2

Le 26 novembre 2018, à 14h.

Directeur de thèse: Emilie Pacary du Neurocentre Magendie, équipe Nora Abrous teamleader: “Neurogénèse et physiopathologie”

 In most areas of the brain, neurons are born during embryogenesis. In contrast, the majority of granule neurons in the dentate gyrus (DG) of the hippocampus are born postnatally and their generation continues throughout adulthood. This finding that new neurons are generated in the adult mammalian brain has opened novel avenues for brain repair and has initiated, in the last 20 years, tremendous efforts to characterize how new neurons differentiate and integrate into adult neural circuitries.
However, further studies are needed to better understand the mechanisms and signaling cascades involved in this process. In this context, we focused on Rnd2, a Rho GTPase particularly enriched in the adult neurogenic DG and described as a key player in the regulation of embryonic cortical neurogenesis.

We found, in vivo, that the deletion of Rnd2 specifically in adult-born hippocampal neurons decreases the survival of these cells, and in the surviving ones, leads to soma hypertrophy, increases dendritic arborization and induces mispositionning. Importantly, this deletion also increases anxiety-like behavior in mice, thus identifying Rnd2 as a critical regulator of adult newborn neuron development and function. In addition, our data show that Rnd2 does not play the same functions in granule neurons born at P0, highlighting a differential regulation of developmental and adult neurogenesis in the DG. In the same vein, we also demonstrate that perinatally-born granule neurons, especially the embryonic ones, are morphologically distinct compared with later-born neurons. Altogether, this PhD work provides new insights into the development of the different populations of granule neurons in the DG, further emphasizing the peculiarity of this brain structure.

Publications

Roberta Azzarelli, Thomas Kerloch, Emilie Pacary. Regulation of cerebral 
cortex development by Rho GTPases: insights from in vivo studies. Front 
Cell Neurosci. (2015) 7;8:445 doi: 10.3389/fncel.2014.00445 (revue).

Thomas Kerloch, Solène Clavreul, Adeline Goron, Djoher Nora Abrous, 
Emilie Pacary. Dentate granule neurons generated during perinatal life 
display distinct morphological features compared with later-born neurons 
in the mouse hippocampus. Cereb. Cortex. (2018) doi: 
10.1093/cercor/bhy224.

Thomas Kerloch, Fanny Farrugia, Marlène Maître, Muriel Koehl, Mylène 
Blanchard, Hélène Doat, Thierry Leste-Lasserre, Julian Ik-Tsen Heng, 
Adeline Goron, Delphine Gonzales, Djoher Nora Abrous, Emilie Pacary. 
Rnd2 is essential for granule neuron development in the adult 
hippocampus and serves a critical role in anxiety-like behavior. En 
préparation.

JURY