TEAM

Polarization and binary cell fate decisions in the nervous system

Group leader : V. Bertrand

We are analyzing how the nervous system is polarized and how this polarity drives the generation of different types of neurons.

FOR BEGINNERS

In both vertebrates and invertebrates, neurons are often generated by asymmetric divisions of neuronal precursors such as neural stem cells. During this process a precursor cell divides asymmetrically to generate two neurons with different identities, or one neuron and a new precursor. Precursor cells are polarized before their division, that is to say that they display two poles with different biochemical properties. During the division the two daughter cells inherite different determinants that give them distinct fates. In the nervous system the polarity of the different neuronal precursors is coordinated implying a communication between the cells.

3D reconstruction of a C. elegans embryo during gastrulation by the Bertrand Team from IBDM, IBDML

3D reconstruction of a C. elegans embryo during gastrulation.

The nematode C. elegans is a good model organism to study these mechanisms. In C. elegans the identity, connectivity and lineage history of every neuron are known. The embryos are transparent and their development can be easily followed by 4D-videomicroscopy. The C. elegans system also offers numerous tools to dissect the molecular basis of biological processes such as forward genetic screens, RNAi screens or transgenesis.

C. elegans embryo at three successive time points using light sheet microscopy (tubulin in green, histone in red).
 

Our team analyses how the nervous system is polarized and how this polarity drives the differentiation of different types of neurons using C. elegans as a model system. Our work has a potential impact on the treatment of some types of cancer as well as on the use of stem cells for cell therapy.

FOR SPECIALISTS

In both vertebrates and invertebrates, postmitotic neurons are often generated by asymmetric divisions of neuronal progenitors such as neural stem cells. This general mechanism used to build the nervous system raises two important questions : how are these asymmetric divisions coordinated in space and how do the daughter cells acquire different fates.

We address these questions using the nematode C. elegans as a model organism. In C. elegans most neurons are generated during neurulation by asymmetric divisions oriented along the antero-posterior axis. We have recently shown that these terminal asymmetric divisions are regulated by a particular Wnt/β-catenin pathway. We are now trying to understand :

Picture showing a C. elegans embryo during gastrulation expressing tubulin::GFP and histone::RFP by the Bertrand Team from IBDM, IBDML

C. elegans embryo during gastrulation expressing tubulin::GFP (green) and histone::RFP (red).

1) How the field of neuronal precursors is polarized. We especially analyze the polarization by a gradient of Wnt ligands and the mechanism establishing this gradient. We address this question in vivo using advanced imaging techniques.

2) How the daughter cells acquire different fates and especially how the asymmetric division machinery is connected to the terminal differentiation program of postmitotic neurons. We analyze more specifically the role of the Wnt/β-catenin pathway and the role played by chromatin factors in this process. We address this question using a combination of automated screens and high-throughput sequencing.

The Wnt/β-catenin pathway is involved in several types of cancer and in the regulation of asymmetric divisions of neural stem cells in vertebrates. This study may therefore help identify candidate target proteins and mechanisms for future anti-cancer drug developments or regenerative medicine treatments.


Main publications

PUBLICATION

Zic-proteins are repressors of dopaminergic forebrain fate in mice and C. elegans.

Tiveron MC, Beclin C, Murgan S, Wild S, Angelova A, Marc J, Coré N, de Chevigny A, Herrera E, Bosio A, Bertrand V, Harold C.
J Neurosci. 2017 Sep 29. pii: 3888-16. PMID: 28972122

PUBLICATION

β-catenin-driven binary cell fate decisions in animal development.

Bertrand V.
Wiley Interdiscip Rev Dev Biol. 2016 Mar 7. PMID: 26952169

PUBLICATION

How targets select activation or repression in response to Wnt

Murgan S, Bertrand V.
Worm. 2015 Sep 1;4(4):e1086869. PMID: 27123368

PUBLICATION

Atypical transcriptional activation by TCF via a Zic transcription factor in C. elegans neuronal precursors.

Murgan S, Kari W, Rothbächer U, Iché-Torres M, Mélénec P, Hobert O, Bertrand V.

Dev Cell. 2015 Jun 22;33(6):737-45. PMID: 26073017

PUBLICATION

Setting-up a simple light sheet microscope for in toto imaging of C. elegans development.

Chardes C., Melenec P., Bertrand V. And Lenne P.F.
J Vis Exp. 2014 May 5;(87). PMID: 24836407

PUBLICATION

Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons.

Bertrand V, Bisso P, Poole RJ, Hobert O.
Curr Biol. 2011 Jul 26;21(14):1225-31. PMID: 21737278

PUBLICATION

Lineage programming: navigating through transient regulatory states via binary decisions.

Bertrand V, Hobert O.
Curr Opin Genet Dev. 2010 Aug;20(4):362-8. PMID: 20537527

PUBLICATION

Analysis of multiple ethyl methanesulfonate-mutagenized Caenorhabditis elegans strains by whole-genome sequencing.

Sarin S, Bertrand V, Bigelow H, Boyanov A, Doitsidou M, Poole RJ, Narula S, Hobert O.
Genetics. 2010 Jun;185(2):417-30. PMID: 20439776

PUBLICATION

Wnt asymmetry and the terminal division of neuronal progenitors.

Bertrand V, Hobert O.
Cell Cycle. 2009 Jul 1;8(13):1973-4. PMID: 19550137

PUBLICATION

Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans.

Bertrand V, Hobert O.
Dev Cell. 2009 Apr;16(4):563-75. PMID: 19386265
Other publications

Interactions

IBDM
NATIONAL
  • Jonathan Ewbank team, Centre d’Immunologie de Marseille-Luminy
INTERNATIONAL
  • Ute Rothbacher team, Innsbruck University, Austria

Funding

Sanofi Aventis funding for V. Bertrand Team from IBDM, IBDML

Labex Inform funding for V. Bertrand team from IBDM, IBDML

 CNRS funding for V. Bertrand Team from IBDM, IBDML  INSERM funding for V. Bertrand Team from IBDM, IBDML

ATIP AVENIR funding for V. Bertrand Team from IBDM, IBDML

Members more

Antoine Barriere     Shilpa Kaur  
Vincent Bertrand
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Vincent Bertrand

Researcher

After a PhD in Marseille on early development of ascidian embryos, he did his postdoc in New York on neuronal differentiation in C. elegans. Since april 2011 he has been in charge of a research group at IBDM working on the mechanisms of polarization and specification during nervous system development using the C. elegans embryo as a model organism.

Antoine Barriere
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Antoine Barriere

Researcher

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Carole Couillault

Technical staff

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Konstantina Filippopoulou

PhD student

Shilpa Kaur
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Shilpa Kaur

PhD student

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Amel Toudji

Technical staff

PhD student on a position funded by FRM. Project: Protein domains and posttranslational modification in the control of Hox protein activity

Overview

Model organism
Biological process studied
  • Polarization and binary cell fate decisions in the nervous system
Biological techniques
  • In vivo advanced imaging
  • Automated screens
  • High-throughput sequencing
Medical application
  • Cancer
  • Cell therapy

Links

Databases on the genetics of C. elegans and related nematodes : Wormbase

Database of behavioral and structural anatomy of C. elegansWormatlas

Open-access collection of original, peer-reviewed chapters covering topics related to the biology of C. elegans : Wormbook