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Régulation de la Transcription au Cours du Développement

Mounia Lagha

Projets de recherche

Gene expression is precisely controlled in time and space during the development of Metazoan organisms. While numerous studies have established how spatial information is integrated by gene regulatory regions, called enhancers, little is known about the temporal aspects of transcription. Most of our insights into gene regulation stem from the use of fixed preparations where timing is artificially reconstituted from different snapshots. Our goal is to integrate the dynamic aspects of transcription to understand how coordination is achieved and whether it is required during development. Transcriptional coordination refers to the inter- nuclear temporal coordination in gene activation (synchrony) and homogeneity in mRNA distribution across a field of coordinately developing cells. Initially we will characterize the mechanisms of transcriptional coordination in the early Drosophila embryo, a model system which allows quantitative imaging and genetic manipulations. However our ultimate goal is to extend these analyses to later stages of development during complex tissue specification.

We are improving the newly available live imaging technique to address fundamental questions about transcriptional dynamics in a multicellular developing embryo, with three main objectives:

  1. Examine the effects of promoter sequence and enhancer priming on transcriptional coordination.
  2. Analyse the inheritance of transcriptional states from mother to daughter cells and identify the bookmarking mechanisms responsible for this memory.
  3. Explore the functional role of transcriptional coordination for cell fate specification during cardiogenesis.

Through the novel integration of the dynamic and quantitative aspects of transcription in a living organism, our research shall connect coordination in transcription to precision in cell specification.

Movie 1: Visualization of transcriptional activation in a living Drosophila embryo
Figure 1: Main objective of the lab

Example of specific projects/recent achievements:  

  1. First visualization of transcriptional memory in a developing multi-cellular embryo.

By monitoring the expression of stochastically expressed transgenes in living Drosophila embryos, we could visualize and quantify the extent to which transcription is inherited from mother to daughter cells (Ferraro et al., Current Biology 2016). Descendants from active mothers activate transcription twice as fast as their neighboring nuclei.

  1. Investigating the mechanisms leading to transcriptional memory.
  2. Deciphering the cis-regulatory sequences responsible for transcriptional synchrony in the early embryo.
  3. Documenting the existence and functional relevance of transcriptional coordination at later stages, during cardiogenesis.
Figure 2: Live imaging of transcription technique
Figure 3: Image analysis pipeline
Figure 4: Transcriptional Memory

Membres

Team leader

Mounia LAGHA

CRCN

+33 (0)4 34 35 96 50

104

Maelle BELLEC

Doctorant

+33 (0)4 34 35 96 50

Matthieu DEJEAN

IE-Recherche

+33 (0)4 34 35 96 50

104

Jeremy DUFOURT

Post-Doc

+33 (0)4 34 35 96 53

Carola FERNANDEZ

Doctorant

+33 (0)4 34 35 96 50

Maelys GICQUEL

AI-Recherche

+33 (0)4 34 35 96 50

Olivier MESSINA

Stagiaire

+33 (0)4 34 35 96 50

Antonio TRULLO

IR-Recherche

+33 (0)4 34 35 96 50

Alumni

Matilde Mantovani (Univ Milan)
Yayoi Wada (Univ.Kyoto)
Quantin Dessables (Univ.Poitiers)
Mathilde Gauchier (Univ.Montpellier)
Louis Redonnet (Ecole Centrale Lyon)
Rachida el Youssfi (Jean Mermoz, Montpellier)
Elisa Atger (S.Weil, Le Puy en Velay)
Hoa Vinh Le (Hanoi University)
Saida Nait Amer (Montpellier University)
Lucas Makinen (Princeton University)

 

Sélection de publications

Autres informations

Financement
2017

ERC starting grant (1 500 000€).

2015-2018

Career Development Award (HFSP) (300.000$)

2016

Grant from the FRM ‘financement d’ingénieur pour le développement d’une technique innovante’.

2015-2018

ATIPE-AVENIR young group leader grant (CNRS/Inserm)

Interactions
At IGMM

E.Bertrand and E.Basyuk: improved MS2 method.

In Montpellier

O.Radulescu and L.Ciandrini (Univ.Montpellier) : mathematical modeling of memory

National and international

M.Harrison (University of Wisconsin Madison, USA): Role of Zelda

K.Jagla and G.Junion (Université Clermont-Ferrand, France): cardiogenesis.

J.Zeitlinger and J.Johnston (Stowers Institute, Kansas City, USA): bioinformatic analysis.

Toutes les équipe de recherche

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Mots-clés
Model organism studied
Drosophila Melanogaster
Biological process
Gene expression, transcriptional dynamics
Biological techniques
Quantitative live imaging, genetics