Gene regulatory networks in Drosophila haematopoiesis and myogenesis

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 Transcriptome analyses of LGs in col mutants and following parasitism (unpublished) revealed the role of JAK-STAT signalling in pro-hemocyte and BMP and Robo signaling in controlling PSC size and morphology.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 Drosophila“ Dubois et al.,  eLIFE 2016 https://elifesciences.org/articles/14979

"Dynamics of transcriptional (re)-programming of syncytial nuclei in developing muscles" Bataillé et al., BMC Biology 2017. https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0386-2

Alary muscles and thoracic alary-related muscles: Atypical striated muscles maintaining the position of internal organs

    The physiological function of an organ depends upon its shape and position within the body.  In addition to body wall muscles, one Alary Muscle (AM) was known to connect the exoskeleton to the heart in every abdominal segment in arthropods. Our team recently discovered the existence of Thoracic Alary-Related Muscles (TARMS) wjhich appose to the respiratory system and connect visceral organs to the skeleton

Boukhatmi et al., Development, 2014  https://dev.biologists.org/content/141/19/3761

Bataille, L. et al., (2015) Mechanisms of Development, 138, 170-176.https://www.sciencedirect.com/science/article/pii/S092547731530006X?via%3Dihub

We have recently shown that the attachment of AMs and TARMs to either circulatory or visceral systems is under the control of Hox genes. ARMs and TARMs are multinucleated sarcomeric muscles which are simultaneously highly deformable and contractile. Genetic ablations of AMs and TARMs demonstrate that thay a new type of muscle connecting the insect exoskeleton to multiple internal organs and ensuring the proper positioning and physiological function of these organs

.Bataille et al., Development 2020 https://dev.biologists.org/content/147/8/dev185645.long ; https://dev.biologists.org/content/147/8/e0807