> Stages de M2 > Liste des stages proposés pour l’année 2014-2015 > Primary cilia in mouse brain development : focus on axonal tract (...)

Primary cilia in mouse brain development : focus on axonal tract defects

proposé par Christine LACLEF , Laboratoire de Biologie du Développement UMR 7622, UPMC-CNRS, INSERM ERL 1156 75005 Paris

Projet de stage :

The goal of this project is to address the role of the primary cilium in different aspects of the brain development in order to better understand how cilia dysfunction leads to a variety of neurodevelopmental disorders in ciliopathies. Structural or functional disruption of the primary cilium causes a large number of congenital syndromes, called ciliopathies, which are multisystem disorders displaying a wide range of clinical features including neurodevelopmental defects. However, our current understanding of how dysfunction of the cilium leads to the clinically observed brain phenotypes remains elusive. Using Ftm/Rpgrip1l knock-out (KO) mice, which recapitulate most phenotypes observed in the most severe ciliopathy, we have previously shown that the major function of primary cilia in early anterior brain patterning is to drive Gli3-R production (Besse et al., 2011). We are now analyzing other brain defects due to cilia disruption, such as the proliferation rate and the migrating behavior of neurogenic progenitors in the telencephalon, as well as cortical neurogenesis and axonal projections (cortico-cortical and corticofugal). Importantly we want to determine the core molecular element lying downstream of the cilium during these developmental processes, with a special attention to the role of Gli3-R.The M2 project will be more specifically dedicated to analyze the axonal projection defects, with a particular attention to the corticofugal fiber tracts. Results of this project should provide a better understanding of the role of Ftm and primary cilia in axonal tract defects, a brain phenotype that has been reported in a severe ciliopathy. So,this work should enlighten the neurodevelopmental origin of a neurological feature of ciliopathies and provide helpful information for prenatal diagnostic of these pathologies.

Techniques mises en œuvre par le stagiaire : Immunofluorescence, hybridation in situ, techniques d’imagerie et d’analyse d’image, dissection et coupes d’embryons de souris (cryostat, microtome, vibratome).

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