Métin
Cortical migration of interneurons
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)
• Justine Masson CR CNRS
• Christine Laclef MC UPMC
• Sophie Scotto MC UPMC
• Melody Atkins Post-doc INSERM
• Anne-Gaëlle Toutain Doctorante
Former members:
• Patricia Gaspar DR1 INSERM, Emérite
• Aude Muzerelle IE INSERM
PAK3 activation promotes the tangential to radial migration switch of cortical interneurons by increasing leading process dynamics and disrupting cell polarity
Viou L, Atkins M, Rousseau V, Launay P, Masson J, Pace C, Murakami F, Barnier JV, Métin C.
Mol Psychiatry. 2024 Mar 7.
PMID:38454080 
CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Atkins M, Wurmser M, Darmon M, Roche F, Nicol X, Métin C.
Nat Commun. 2023 Dec 4;14(1):8003.
PMID:38049397
YIF1B mutations cause a post-natal neurodevelopmental syndrome associated with Golgi and primary cilium alterations
Diaz J, Gérard X, Emerit MB, Areias J, Geny D, Dégardin J, Simonutti M, Guerquin MJ, Collin T, Viollet C, Billard JM, Métin C, Hubert L, Larti F, Kahrizi K, Jobling R, Agolini E, Shaheen R, Zigler A, Rouiller-Fabre V, Rozet JM, Picaud S, Novelli A, Alameer S, Najmabadi H, Cohn R, Munnich A, Barth M, Lugli L, Alkuraya FS, Blaser S, Gashlan M, Besmond C, Darmon M, Masson J.
Brain. 2020 Oct 1;143(10):2911-2928
PMID:33103737
How early life impacts emotional behaviour in adulthood.
Teissier A, Gaspar P.
Med Sci (Paris). 2020 Mar;36(3):218-221.
PMID:32228838
FIGNL1 associates with KIF1Bβ and BICD1 to restrict dynein transport velocity during axon navigation.
Atkins M, Gasmi L, Bercier V, Revenu C, Del Bene F, Hazan J, Fassier C.
J Cell Biol. 2019 Oct 7;218(10):3290-3306.
PMID:31541015
Early-life stress impairs postnatal oligodendrogenesis and adult emotional behaviour through activity-dependent mechanisms.
Teissier A, Le Magueresse C, Olusakin J, Andrade da Costa BLS, De Stasi AM, Bacci A, Imamura Kawasawa Y, Vaidya VA, Gaspar P.
Mol Psychiatry. 2019 Aug 22.
PMID:31439936
Topographical cues control the morphology and dynamics of migrating cortical interneurons.
Leclech C, Renner M, Villard C, Métin C.
Biomaterials. 2019 Sep;214:119194.
PMID:31154150
Protein interacting with Amyloid Precursor Protein tail-1 (PAT1) is involved in early endocytosis.
Dilsizoglu Senol A, Tagliafierro L, Gorisse-Hussonnois L, Rebeillard F, Huguet L, Geny D, Contremoulins V, Corlier F, Potier MC, Chasseigneaux S, Darmon M, Allinquant B.
Cell Mol Life Sci. 2019 Dec;76(24):4995-5009.
PMID:31139847
The Ciliopathy Gene Ftm/Rpgrip1l Controls Mouse Forebrain Patterning via Region-Specific Modulation of Hedgehog/Gli Signaling.
Andreu-Cervera A, Anselme I, Karam A, Laclef C, Catala M, Schneider-Maunoury S.
J Neurosci. 2019 Mar 27;39(13):2398-2415.
PMID:30692221
RPGRIP1L is required for stabilizing epidermal keratinocyte adhesion through regulating desmoglein endocytosis.
Choi YJ, Laclef C, Yang N, Andreu-Cervera A, Lewis J, Mao X, Li L, Snedecor ER, Takemaru KI, Qin C, Schneider-Maunoury S, Shroyer KR, Hannun YA, Koch PJ, Clark RA, Payne AS, Kowalczyk AP, Chen J.
PLoS Genet. 2019 Jan 28;15(1):e1007914.
PMID:30689641
