Métin

Cortical migration of interneurons: Role of Sonic Hedgehog and of the primary cilium
PI : Christine Métin

The cortical GABAergic neurons are inhibitory interneurons that play an essential role in cortical function to control neuronal excitability. Altered development of interneurons have been implicated in pathologies such as epilepsy, mental retardation, and schizophrenia. During embryonic life, interneurons migrate over long distances before reaching the cortex as they are generated outside the cortex in ventral forebrain regions called the ganglionic eminences. We have previously demonstrated that GABA interneurons assemble a primary cilium during their migration and that this cilium is involved in the direction of migratory trajectories by mechanisms that are still unknown. Moreover, Sonic Hedgehog (Shh) influences the migration of interneurons in part via signal transduction at the cilium.

Our current projects aim to understand how Shh and the primary cilium control the migration of GABA interneurons and the establishment of local inhibitory circuits. (transcriptional regulation, local signaling, etc). Beside studies in mouse mutants, we are using in vitro approaches to further characterize the influence of biochemical and physical factors on the migratory properties of interneurons.

Figure 1 : (A) Scheme of a coronal section from the left hemisphere of a mouse embryo illustrating the trajectories of GABAergic neurons born in the medial ganglionic eminence (MGE) toward the developing cortex: tangential migration pathways in blue and green, radial trajectories in yellow. (B) Immunostaining (in green) of the primary cilium of a MGE neuron (in red) migrating on a substrate of cortical cells (nuclei in blue). (C) A genetic ablation of the primary cilium or an application of cyclopamine (Sonic hedgehog –SHH- pathway inhibitor) maintains MGE neurons in their tangential migration pathway, whereas an application of SHH promotes their exit from the tangential pathway (From Pedraza & Métin, 2014).

Team Composition

Team leaders : Christine Métin (DR2 INSERM)
• Patricia Gaspar DR1 INSERM, Emérite
• Justine Masson CR CNRS
• Christine Laclef MC UPMC
• Sophie Scotto MC UPMC
• Aude Muzerelle IE INSERM
• Melody Atkins Post-doc INSERM
• Anne-Gaëlle Toutain Doctorante