Neurodevelopment : Temporal functions of transcription factors in mouse brain development

Development of the central nervous system relies on a timely organized network of gene and cellular interactions. A handful of signalling pathways and transcription factors are repetitively used to generate more and more specialized structures. How a limited number of molecular actors can generate so many different forms ? To address this question, our team focuses on an essential homeobox transcription factor, Otx2, whose expression is highly dynamic throughout brain development. Our basic research may also have clinical implications: on the one hand, human Otx2 mutations are associated to severe development abnormalities, including prosencephaly, microphtalmia, and retina degeneration, and, on the other hand, Otx2 overexpression is found in 80% of medulloblastomas, which are aggressive paediatric neural cancers. We use advanced mouse genetics methods, such as self-knockout, combined to genomic analyses to understand the various modes of action of this transcription factor during pre- and post-natal development.

Current research :

Activities in the cerebellum

We use mouse lines to monitor in vivo expression of the Otx2 gene, to trace the Otx2 lineage at any stage of cerebellum development and to perform conditional gene ablation. With these tools, we are addressing the developmental origin of cerebellar neurons and how Otx2 controls their proliferation.

 

 

Genetic functions in adult retina

Self knockout in adult retina triggers slow photoreceptor degeneration, revealing complex late functions of Otx2. We take advantage of the thorough and temporally controlled genetic damage to perform time-lapse profiling of the retinal transcriptome to identify the gene network governed by Otx2. ChIP-Seq analyses are carried out to pin down Otx2 targetome. Cell-specific gene knockdown of candidates may help discover new mechanisms of eye diseases.


 

 

Importance of spatial and temporal gene restriction

Otx2 expression pattern is very dynamic during development, with successive phases of expansion, regionalization and down-regulation in different areas of the embryo. We explore how much gene extinction is necessary for proper development. Using genetic tricks, we delay Otx2 expression in brain areas that should turn it off and investigate the fate of these brain parts.

 

Last publications

Deletion of OTX2 in neural ectoderm delays anterior pituitary development. - 2015 - Human molecular genetics - 24 P939-53 - Mortensen AH, Schade V, Lamonerie T, and Camper,SA

Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons. - 2015 - Cell reports - 13 P990-1002 - Kim HT, Kim SJ, Sohn YI, Paik SS, Caplette R, Simonutti M, Moon KH, Lee EJ, Min KW, Kim MJ, Lee DG, Simeone A, Lamonerie T, Furukawa T, Choi JS, Kweon HS, Picaud S, Kim IB, Shong M, and Kim,JW

Comprehensive interactome of Otx2 in the adult mouse neural retina. - 2015 - Genesis (New York, N.Y. : 2000) - 53 P685-94 - Fant B, Samuel A, Audebert S, Couzon A, El Nagar S, Billon N, and Lamonerie,T

Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea. - 2015 - Development (Cambridge, England) - 142 P2792-800 - Vendrell V, Lì³pez-Hernández I, Durán Alonso MB, Feijoo-Redondo A, Abello G, Gálvez H, Giráldez F, Lamonerie T, and Schimmang,T

Otx2 ChIP-seq Reveals Unique and Redundant Functions in the Mature Mouse Retina. - 2014 - PloS one - 9 Pe89110 - Samuel A, Housset M, Fant B, and Lamonerie,T

Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development. - 2014 - Development (Cambridge, England) - 141 P166-75 - Fauquier T, Chatonnet F, Picou F, Richard S, Fossat N, Aguilera N, Lamonerie T, and Flamant,F

Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm. - 2014 - Development (Cambridge, England) - 141 P3859-67 - Ip CK, Fossat N, Jones V, Lamonerie T, and Tam,PP

Loss of Otx2 in the adult retina disrupts retinal pigment epithelium function, causing photoreceptor degeneration. - 2013 - The Journal of neuroscience : the official journal of the Society for Neuroscience - 33 P9890-904 - Housset M, Samuel A, Ettaiche M, Bemelmans A, Béby F, Billon N, and Lamonerie,T

The homeobox gene Otx2 in development and disease. - 2013 - Experimental eye research - 111 P9-16 - Beby F, and Lamonerie,T

ES cell-derived renewable and functional midbrain dopaminergic progenitors. - 2011 - Proceedings of the National Academy of Sciences of the United States of America - 108 P9703-8 - Chung S, Moon JI, Leung A, Aldrich D, Lukianov S, Kitayama Y, Park S, Li Y, Bolshakov VY, Lamonerie T, and Kim,KS

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Lamonerie Thomas
Group Leader

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Members Team
Researchers
   Billon Nathalie
   D`Autréaux Fabien
Postdocs
   Ruiz Reig Nuria
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   El Nagar Salsabiel
   Pensieri Pasquale
Engineers & Technicians
   Alves Joffrey
   Mantilleri Annabelle
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JOB OFFERS

    February 2017 - T. Lamonerie Team
   1 CDD Position IE 2 ans   Closed

    January 2017 - T. Lamonerie Team
   1 CDD Technicien AI Biologiste 3 ans   Closed

    September 2014 - T. Lamonerie Team
   CDD Technicien AI Biologiste   Closed

    January 2014 - T. Lamonerie Team
   1 Post-Doc position   Closed

    January 2014 - T. Lamonerie Team
   1 CDD Technicien/Ingénieur   Closed

    November 2008 - T. Lamonerie Team
   1 Lab technician CDD   Closed

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CNRS UMR7277, Inserm U1091, UNS Université Nice Sophia Antipolis
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