Developmental mechanisms of brain disorders

Leader

Co-Leaders

Research center

17 rue du Fer à Moulin
75005 Paris

Institution

Inserm
Université Pierre et Marie Curie
Labex BIOPSY
ED158
Université Pierre et Marie Curie

Laboratory

Coutures Marianne
Phone: 33(0) 1 45 87 61 28
Fax: 33(0)145 87 61 35
UMRS 839

Keywords

migration
Cortex
Retina
serotonin
axon guidance
Neural activity
Critical periods
 

Publications

Fernandez SP, Muzerelle A, Scotto-Lomassese S, Barik J, Gruart A, Delgado-García JM, Gaspar P. Constitutive and Acquired Serotonin Deficiency Alters Memory and Hippocampal Synaptic Plasticity. Neuron. 2016 Oct 19;92(2):435-448. doi: 10.1016/j.neuron.2016.09.020. 

Muzerelle A, Scotto-Lomassese S, Bernard JF, Soiza-Reilly M, Gaspar P. (2014) Conditional anterograde tracing reveals distinct targeting of individual serotonin cell groups (B5-B9) to the forebrain and brainstem. Brain Struct Funct. 2014 Nov 18

 Assali A, Gaspar P, Rebsam A. Activity dependent mechanisms of visual map formation--from retinal waves to molecular regulators. Semin Cell Dev Biol. 2014 Nov;35:136-46 

Luccardini C, Hennekinne L, Viou L, Yanagida M, Murakami F, Kessaris N, Ma X,  Adelstein RS, Mège RM, Métin C. ( 2013) N-cadherin sustains motility and polarity of future cortical interneurons during tangential migration. J Neurosci. 2013 Nov 13;33(46):18149-60.

Diaz S.L*, Narboux-Nême N*, Trowbridge S,  Scotto, S, Borgemann FK, Jessberger S, Giros B , Maroteaux L, Deneris E, Gaspar P (2013) Paradoxical increased survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin. Eur J Neuroscience. 38:2650-8.

Baudoin_ JP*, Viou* L, Launay P-S, Luccardini C, Espeso S, Kiyasova V, Irinopoulou T , Alvarez C,  Rio J-P, Boudier T, Lechaire J-P, Kessaris N,  Spassky N, Métin C. (2012) Tangentially migrating neurons assemble a primary cilium that promotes their re-orientation to the cortical plate. Neuron , 20;76 :1108-22. (* equal contribution).

Narboux-Nême N, Evrard A, Ferezou I, Erzurumlu RS, Kaeser PS, Lainé J, RossierJ, Ropert N, Südhof TC, Gaspar P. (2012) Neurotransmitter release at the thalamocortical synapse instructs barrel formation but not axon patterning in the somatosensory cortex. J Neurosci., 32:6183-6196.

Rebsam A, Bhansali P, Mason CA (2012) Eye-specific projections of retinogeniculate axons are altered in albino mice. J Neurosci  32(14): 4821-6

Narboux-Nême N, Angenard G, Mosienko V, Klempin F, Pitychoutis PM, Deneris E, Bader M, Giros B, Alenina N, Gaspar P. (2013) Postnatal growth defects in mice with constitutive depletion of central serotonin. ACS Chem Neurosci. ;4:171-81

Fields of research

Neurogenetics / neurodevelopment

Research Theme

A number of developmental disorders, in particular in the field of psychiatry and neurology, are thought to result from brain wiring defects. This is the case for mental retardation or autism-spectrum disorders, but also concerns non-cognitive pathologies such as visual defects in albinism. Formation of brain circuits is a complex process implying many sequential steps from the generation of neurons, their migration and axonal growth, and the establishment of selective synaptic connections. Refinement and consolidation of neural circuits continue during late periods of development, after birth, when the brain is the most plastic and likely to be modified by the environment with lasting effects on behaviour. Research in the team aims to understand the molecular mechanisms underlying the formation of brain circuits, along 3 main themes :

1° Migration of cortical interneurons : this theme is led by Christine Métin, focusing on the role of sonic hedgehog in cilia , using advanced live imaging methods.

2° Development of retinal visual pathways : this theme is led by Alexandra Rebsam focusing on the role of axon guidance molecules, neural activity and and neurotransmission in the establishment of visual maps. For more information, www.rebsam.org

3° Development of serotonin systems : this theme is led by Patricia Gaspar, focusing on the development of raphe and prefrontal cortical circuits influenced by serotonin and the effects of early life stress.



ENP Students

Jimmy OLUSAKIN

Team members

Sophie SCOTTO
Aude MUZERELLE
Mariano SOIZA-REILLY
Anne TEISSIER
Cédric FRANCIUS
Teng TENG
Claire LECLECH
Maria PEDRAZA
Delphine PRIEUR
Alexandra REBSAM

Lab rotation

Developmental defects of the visual system in albinism

Team leader: 

GASPAR Patricia

Dates: 

September 18, 2017 - June 29, 2018

Application deadline: 

June 29, 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

~ April-June 2018

Project

Brain function relies on the precise organization of neuronal connections during development. Alterations of any of these steps will have structural and functional consequences. We use the visual system to precisely study the mechanisms that regulate some of these developmental events and this project focuses on a rare disease, albinism, showing clear functional consequences arising from a developmental alteration. In albinism, a defect in melanin production leads to hypopigmentation, a hallmark of this disease, but also to important visual deficits due to abnormal development of the retina. This project aims to characterize the links between melanin production and retinal specification during development and their consequences on neuronal connections and activity within the retina. Furthermore, we will decipher how the albino mutation at the level of the retinal pigmented epithelium impact retinal development. For that, we will use a combination of in vivo approaches in mouse models and in vitro approaches. The student will use immunohistochemistry, fluorescence and confocal microscopy, calcium imaging and videomicroscopy as well as cell culture techniques. This study will shed lights on the pathophysiology of albinism and unravel mechanisms governing normal retinal development and visual neural circuit formation.

Contact

Institut du Fer à Moulin - 17 rue du fer à moulin 75005 Paris - +33 1 45 87 61 27 - alexandra.rebsam@inserm.fr


Supervisor: 

REBSAM Alexandra

Analysis of the migration of embryonic neurons in micropatterned environments

Team leader: 

METIN Christine

Dates: 

September 18, 2017 - June 29, 2018

Application deadline: 

June 29, 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

~ April-June 2018

Project

Our laboratory recently showed that the topography of the micro-environment influences the migratory properties of immature cortical interneurons. Interneurons migrating among round or square plots strongly differ in morphology and dynamics.  The stage will aim at characterizing the organization of the cytoskeleton (microtubules, acto-myosin) in interneurons migrating on each type of substrate using superresolution microscopy and live cell imaging. 

Contact

Institut du Fer à Moulin - 17, rue du fer à moulin 75005 Paris - +33 1 45 87 61 26 - Christine.metin@inserm.fr

Supervisor: 

METIN Christine