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

Team members

Researcher

Laetitia Bataille
Michelle Crozatier-borde
Laurence Dubois
Jean-louis Frendo
Nathalie Vanzo
Alain Vincent
Ismael Morin poulard

Associate professor

Gaelle Le breton

Technical staff

Yannick Carrier
Amelie Destenabes
Julien Favier
Caroline Monod
Aurore Pelletier

PhD student

Manon Destalminil-letourneau
Yushun Tian

Master student

Jeremy Castagne

Presentation

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. The historical entry point to these projects was the involvement of Collier (Col), the Drosophila ortholog of vertebrate Early B-Cell Factor (EBF). Col and EBF defined of a novel family of metazoan transcription factors, the COE proteins, characterized by a specific DNA binding domain.

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 Transcriptome analyses of LGs in col mutants and following parasitism (unpublished) revealed the role of JAK-STAT signalling in pro-hemocyte and BMP and Robo signaling (submitted) in controlling PSC size and morphology.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.

Building the muscle pattern; Specification and realization of muscle identity

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 Cells (FC) with naïve myoblasts. FCs originate from muscle progenitor cells (PCs) specified at fixed position and time within the somatic mesoderm. Our laboratory contributed to show that muscle 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 recruited naive myoblasts upon fusion. We recently genetically identified new iTFs. This provided a novel, dynamic view of the transcriptional control of muscle identity, including lineage-specific regulatory loops connecting evolutionarily conserved identity and general myogenic Transcription Factors (submitted).
Ongoing work aims at identifying muscle identity realisator genes, using genome-wide profiling and computational approaches -TF and Cis-Regulatory Modules-, and understanding how the generic myogenic and muscle identity programs are coordinated to generate the stereotypical muscle pattern.

Article under revision (05 2016): “Integrating transcriptional dynamics of muscle identity and differentiation programs during Drosophila muscle development“

Article under revision (05 2016) “Genetic dissection of the Transcription Factor code controlling serial specification of muscle identities in Drosophila“

The Thoracic Alary-Related Muscles; A novel type of deformable muscles. (see new project)