TEAM

Polarization and binary cell fate decisions in the nervous system

Group leader : V. Bertrand

We are analyzing how the divisions of neuronal progenitors are regulated and how differentiated neurons are produced in a robust manner.

FOR BEGINNERS

Neurons are often generated by asymmetric divisions of neuronal progenitors such as neural stem cells. During this process, a progenitor cell divides asymmetrically to generate two neurons with different identities, or one neuron and a new progenitor. In the nervous system, the asymmetric divisions of the different progenitors are tightly coordinated, implying a communication between cells. In addition, during nervous system development, a very precise set of different neuronal types is produced, meaning that their specification process has to be very robust.

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.

Our team analyzes how the asymmetric divisions of neuronal progenitors are controlled and how various differentiated neuron types are produced in a robust manner. To address these questions we are using the nematode C. elegans as a model organism. C. elegans is a good system to study this process as its nervous system is simple and well characterized. In addition, in C. elegans, the lineage history of every neuron is 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 genome-wide screens, transgenesis or CRISPR genome engineering.

By characterizing the mechanisms controlling neuronal progenitor divisions and differentiation, our work may have an impact on the development of treatments against some types of cancer or neurodegenerative diseases.

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 in a robust manner.

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 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 progenitors is polarized (upstream of the asymmetric divisions). We have recently observed that Wnt ligands, expressed at a higher level in the posterior of the embryo, regulate this process. We are now analyzing how these Wnt ligands polarize the neuronal progenitors using advanced in vivo imaging techniques with single molecule resolution.

2) How the daughter cells acquire different neuronal fates in a reliable manner (downstream of the asymmetric divisions). More precisely, we analyze how the Wnt/β-catenin pathway is connected to the terminal differentiation programs and have identified a novel mode of action for TCF, the key transcription factor of the Wnt pathway. We are also characterizing the mechanisms that allow this cell fate specification process to be highly robust and, in particular, the contribution of chromatin factors. We address this question using a combination of CRISPR genome engineering, in vivo quantitative imaging and single molecule RNA FISH.

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.


Selected publications

PUBLICATION

Neuronal specification in C. elegans: combining lineage inheritance with intercellular signaling

Barrière A, Bertrand V.
J Neurogenet. 2020 Jun 30:1-9. doi: 10.1080/01677063.2020.1781850. PMID: 32603241

PUBLICATION

Wnt ligands regulate the asymmetric divisions of neuronal progenitors in C. elegans embryos

Shilpa Kaur, Pauline Mélénec, Sabrina Murgan, Guillaume Bordet, Pierre Recouvreux, Pierre-François Lenne, Vincent Bertrand
Development 2020 147: dev183186 doi: 10.1242/dev.183186 Published 6 April 2020 PMID: 32156756

PUBLICATION

Zic Genes in Nematodes: A Role in Nervous System Development and Wnt Signaling.

Bordet G, Bertrand V.
Adv Exp Med Biol. 2018;1046:59-68. doi: 10.1007/978-981-10-7311-3_4. PMID: 29442317

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

Sumeet Sarin, Vincent Bertrand, Henry Bigelow, Alexander Boyanov, Maria Doitsidou, Richard J Poole, Surinder Narula, Oliver Hobert
Genetics . 2010 Jun;185(2):417-30. doi: 10.1534/genetics.110.116319. Epub 2010 May 3. 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

Members more

khulganaa Buyannemekh Antoine Barriere     Sabrina Murgan Fabien Soulavie  
Vincent Bertrand
Close window
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.

khulganaa Buyannemekh
Close window
khulganaa Buyannemekh

PhD student

Antoine Barriere
Close window
Antoine Barriere

Researcher

Close window
Carole Couillault

Technical staff

Close window
Konstantina Filippopoulou

PhD student

Sabrina Murgan
Close window
Sabrina Murgan

Researcher

After a PhD on Xenopus development in Buenos Aires, she joined the team as a postdoc in november 2012. She is working on the transcriptional mechanisms that link asymmetric division of neuronal precursors to neuronal differentiation of postmitotic neurons.

Fabien Soulavie
Close window
Fabien Soulavie

Postdoctoral fellow

Close window
Amel Toudji-zouaz

Technical staff

Overview

Model organism
Biological process studied
  • Polarization of neuronal precursors and differentiation of neurons
Biological techniques
  • In vivo advanced imaging
  • Single molecule RNA FISH
  • CRISPR genome engineering
  • Automated screens
Medical application
  • Cancer
  • Neurodegenerative diseases
  • Cell therapy

Links

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

Database of anatomy of C. elegansWormatlas

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