Invited Seminar

11:30 am, TAGC meeting room.

July 8 - Dominic Van Essen, IRCAN team 'transcription specificity', Institute for Research in Cancer & Ageing, Nice, "Regulating enhancer and...


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Latest publications

Potier D, Seyres D, Guichard C, Iche-Torres M, Aerts S, Herrmann C, Perrin L. Identification of cis-regulatory modules encoding temporal dynamics during development. BMC...


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Home Research Developmental networks L. Perrin

Laurent Perrin

 

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+33 4 91 26 96 12

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Research interest

How do cardiac cells, once specified, acquire their particular fate and function? Our research projects focuse on the molecular mechanisms of cardiac differentiation, taking advantages of Drosophila to provide a systems biology understanding of the process.

 

Mechanisms of cardiac differentiation

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Cardiogenesis in Drosophila constitutes a well comprehended and documented example of organogenesis in which the function of a number of regulatory factors (Transcription Factors (TFs) or signaling pathways) has been thoroughly studied and described. The Drosophila cardiac system has long been recognized as homologous to the cardiovascular system of vertebrates, in particular because conserved TFs are involved in cardiac development in both fly and vertebrates. The implication of these TFs in a variety of cardiac diseases highlights the need to acquire an in depth understanding of their functions.

 

dynamqiqueIn the past years, our goal has been to analyse the genetic control of embryonic and adult cardiomyocytes differentiation (Perrin et al 2004: Monier et al 2005). and  to set up functional genomics approaches to analyse cardiac tube formation (Zeinouti et al 2007; Salmand et al 2011). We also developed physiological and cellular approaches to analyze cardiac function, which allows measuring in vivo the functional consequences of gene invalidations (Lalevée et al 2006; Sénatore et al 2010).

 

Current projects aim at providing a holistic view of the genetic networks which control cardiac differentiation. How do conserved coeur embryonTFs dynamically interact to control the successive steps driving progressively the differentiation of the cardiomyocytes? What are the downstream gene networks controlled by these TFs? These questions are the main issues we want to tackle. The objectives are to generate and integrate genome-wide qualitative and quantitative data to dissect the GRN that dynamically controls the progressive differentiation of the cardiac system. This project is done in close collaboration with several european laboratories (see Modheart webpage).

 

We are also interested in investigating how effectors genes in the network produce the phenotype. Specifically, in colaboration with Nathalie Lalevée, our goal is to understand the mechanisms by which the cardiac function is acquired and regulated, in particular during mechanosensation (Sénatore et al 2010), a process in which cells sense and respond to mechanical strain.

In addition, to investigate how the cardiac function is maintained at adulthood, we have recently launched a data driven approach to unravel the genetic control of cardiac aging. This lead to the identification of several  transcription factors and signalling pathways (Monnier et al, in press), whose precise function and activation during cardiac aging is currently under investigation.

 

These integrated approaches take advantage of our joined competences in genetics, genomics, cell biology and physiology and benefits from the bioinformatics competencies developed in the lab.

coeur fermé

 

Group Members & Internal collaborators

  • Laurent Perrin;   Research associate, CNRS
  • Laurence Röder; Lecturer Université Aix-Marseille
  • Arnaud Defaye;  PostDoc
  • Denis Seyres;  PhD student
  • Céline Guichard; Ingeneer

 

Funding

ANR Young Investigator / EraSysbio / Association Française contre les Myopathies / Fondation pour la Recherche Médicale/ Université de la Méditerranée

Relevant Publications

- Monnier, V., Iché-Torres, M., Rera, M., Contremoulins, V., Guichard, C., Lalevée, N., Tricoire, H., and Perrin, L. dJun and Vri/dNFIL3 are major regulators of cardiac aging in Drosophila. PLoS Genetics. In press.
- Seyres D, Röder L, Perrin L. Genes and networks regulating cardiac development and function in flies: genetic and functional genomic approaches. Brief Funct Genomics. 2012 Sep;11(5):366-74.
- Merabet S, Litim-Mecheri I, Karlsson D, Dixit R, Saadaoui M, Monier B, Brun C, Thor S, Vijayraghavan K, Perrin   L, Pradel J, Graba Y. (2011) Insights into Hox protein function from a large scale combinatorial analysis of protein domains. PLoS Genet. 2011 Oct;7(10):e1002302.
- Salmand PA, Iché-Torres M, Perrin L. Tissue-specific cell sorting from Drosophila embryos: application to gene expression analysis. Fly (Austin). 2011 Jul-Sep;5(3):261-5.
- Sénatore, S., Rami Reddy, V., Sémériva, M., Perrin, L. and Lalevée, N. (2010). Response to Mechanical Stress Is Mediated by the TRPA Channel Painless in the Drosophila Heart. PLoS Genet. 6 (9). pii: e1001088
- Medioni C, Sénatore S, Salmand PA, Lalevée N, Perrin L, Sémériva M. The fabulous destiny of the Drosophila heart Curr Opin Genet Dev. (2009) 19(5):518-25. (review)
 - Babcock DT, Brock AR, Fish GS, Wang Y, Perrin L, Krasnow MA, Galko MJ (2008). Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae. Proc Natl Acad Sci U S A 105: 10017-22.
- Occor K, Perrin L, Lim HY, Qian L, Wu X, Bodmer R. Genetic control of heart function and aging in Drosophila. Trends Cardiovasc Med. (2007) 17(5):177-82. (review)
- Monier B, Tevy MF, Perrin L, Capovilla M and Sémériva M. Downstream of Homeotic genes: In the heart of Hox Function. Fly (2007) 1, 59-67. (review)
- Zeitouni B, Sénatore S, Séverac D, Aknin C, Sémériva M, Perrin L (2007). Signalling pathways involved in adult heart formation revealed by gene expression profiling in Drosophila. PLoS Genet 3: 1907-21.
-  Lalevée N, Monier B, Sénatore S, Perrin L, Sémériva M (2006). Control of cardiac rhythm by ORK1, a Drosophila two-pore domain potassium channel. Curr Biol 16: 1502-8.
- Monier B, Astier M, Sémériva M, Perrin L (2005). Steroid-dependent modification of Hox function drives myocyte reprogramming in the Drosophila heart. Development 132: 5283-93.
- Perrin L, Monier B, Ponzielli R, Astier M, Sémériva M (2004). Drosophila cardiac tube organogenesis requires multiple phases of Hox activity. Dev Biol 272: 419-31.