Gene regulatory networks in Drosophila haematopoiesis and myogenesis

Alain VINCENT

Michelle CROZATIER-BORDE


DR CNRS
05 61 55 82 89

DR CNRS
05 61 55 82 90

Membres de l'équipe

  Chercheur
  • Laurence DUBOIS
  • Jean-Louis FRENDO
  • Nathalie VANZO
  Enseignant/chercheur
  • Gaëlle LE BRETON
  Soutien technique
  • Yannick CARRIER
  • Caroline MONOD
  Etudiant en Thèse
  • Alexandre CARAYON
  • Manon DESTALMINIL-LETOURNEAU

Présentation

Cell identity is progressively established along animal development by the intertwining of transcriptional regulatory cascades and cell signaling pathways. Our team’s research focuses on two developmental programs in Drosophila : i) Larval hematopoiesis and cellular immune responses ; ii) Specification and realization of muscle identity.

Hematopoieis and cellular immune responses to parasitism.

The Drosophila immune defense relies upon synthesis of anti-microbial peptides and activity of circulating cells, the hemocytes. Larval hematopoiesis takes place in a specialized organ, the lymph gland (LG). Our lab discovered a few years ago that Col was required for specification of the Posterior Signalling Center (PSC) in the LG and the production of lamellocytes, a cryptic hemocyte type, upon wasp parasitism. The PSC was then proposed to control, in a non cell autonomous manner, hemocyte homeostasis in the LG, reminiscent of the vertebrate hematopoietic niche in the bone marrow. Transcriptome analyses of LGs in col mutants and following parasitism (unpublished) revealed the role of JAK-STAT signalling in pro-hemocyte and BMP and Robo signaling in controlling PSC size and morphology. While the PSC contributes to LG homeostasis by regulating blood cell differentiation, col cell autonomously maintains a core population of LG progenitors. Lineage tracing further indicated that the hematopoietic progenitor population is heterogenous.
Our current projects focus on identifying parameters of prohemocyte plasticity, including the role of the vascular system, and how the PSC controls the cellular immune response to parasitism. Genetic manipulation of different cell types in the LG is expected to provide novel insight into the communication between the niche(s) and hematopoietic stem cells and progenitors in the mammalian bone marrow.

Recent publications : Morin-Poulard, I., Sharma, A., Louradour, I., Vanzo, N., Vincent, A. and Crozatier, M.  Nature communications. 2016

Reactive oxygen species-dependent Toll/NF-κB activation in the Drosophila hematopoietic niche confers resistance to wasp parasitism  I. Louradour, A. Sharma, I. Morin-Poulard, M. Letourneau, A. Vincent, M. Crozatier and N. Vanzo  .  eLIFE 2017
 

Building a stereotyped muscle pattern; Specification and realization of muscle morphology

Textbook drawings of human anatomy illustrate the morphological diversity of body muscles allowing precision and strength of movements. Each Drosophila skeletal muscle displays a specific morphological identity (size, shape, orientation, innervation) and forms by fusion of a Founder Cell (FC) with naïve myoblasts. FCs originate from muscle progenitor cells (PCs). Our laboratory contributed to show that muscle morphological  identity reflects the expression by each PC/FC of a specific combination of “identity” Transcription Factors, and integrates temporal, positional and homeotic information. Transcriptional identity is then propagated to the nuclei of fusing naive myoblasts, in parallel to implementation of muscle differentiation (Bataillé et al., 2017). We recently genetically identified new iTFs. This  provided a novel, dynamic view of the transcriptional control of muscle identity, by combinatorial inputs from lineage-specific TFs, e.g., Col/EBF, Tup/Islet1,  and  general myogenic Transcription Factors, e.g., Eya, Six, Nau/MyoD (Dubois et al., 2016).
Ongoing work aims at identifying muscle identity realisator genes, using genome-wide profiling and computational approaches and studying the physiological consequences of specifc muscle pattern defects gnerated by genome editing.

Recent publications :

Genetic dissection of the Transcription Factor code controlling serial specification of muscle identities in DrosophilaDubois et al.,  eLIFE 2016

"Dynamics of transcriptional (re)-programming of syncytial nuclei in developing muscles" Bataillé et al., BMC Biology 2017.

 

The Thoracic Alary-Related Muscles; A novel type of internal muscles.

            In addition to body wall muscles, one Alary Muscle (AM) connects the exoskeleton to the heart in every abdominal segment. Our team recently discovered the existence of Thoracic Alary-Related Muscles (TARMS). TARMs appose to the respiratory system and connect visceral organs to the skeleton. Boukhatmi, H. , Schaub, C., Bataillé, L., Reim, I., Frendo J.L., Frasch, M.* and Vincent, A.*..An Org1/Tbx1-Tup/Islet1 transcriptional cascade reveals the existence of different types of alary muscles connecting internal organs in Drosophila. . Development, 2014               

We propose that TARMs are novel type of muscles connnecting internal organs and playing an architectural role in sensing organ position ( similar to abseiling ropes).

A novel project of our lab is studying the development, function and innervation of TARMs, including live imaging and locomotion behavior tests, within and Evo/Devo framework.

Recent review : Bataille, L. et al., (2015) Mechanisms of Development, 138, 170-176.

 

 

Projets

The Thoracic Alary-Related Muscles; A novel type of deformable muscles.

Publications

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Financements

     

Anciens membres

Université Paul Sabatier
118 Route de Narbonne

31062 TOULOUSE Cedex
France

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