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MECANISMES DE REGULATION
DE L'HEMATOPOÏESE EMBRYONNAIRE
CHEZ LA DROSOPHILE

Abstract : Haematopoietic development provides an excellent paradigm to address how multipotent
cells generate a spectrum of cell types through the combinatorial action of transcription factors.
During this process, the blood cells progenitors proliferate and differentiate to give rise to
different specialised blood cell types. Despite the evolutionary distance between Drosophila and
vertebrates, many of the molecular pathways governing haematopoiesis have been conserved. In
particular, transcription factors of the GATA, FOG (Friend Of GATA) and RUNX families,
which regulate several steps of haematopoiesis in vertebrates, also control Drosophila
haematopoiesis. Thus, the fruit fly may provide a valuable model system to gain insight into the
mechanisms of blood cell lineage formation in vivo. In Drosophila embryo, the blood cell
progenitors (prohemocytes) give rise to two terminally differentiated cell types : plasmatocytes
and crystal cells. We have investigated the mechanisms of regulation of this process during
Drosophila embryonic development.
First, we have analysed the function and the mechanism of action of the GATA
transcription factor Serpent (Srp) that is required for blood cell precursor specification and for
the formation of the two populations of blood cells (plasmatocytes and crystal cells). We have
shown that serpent encodes different isoforms that have different activities during this process.
Furthermore we have shown that the activity of Srp is modulated by different cofactors during
haematopoiesis. Notably, Srp is able to recruit the FOG cofactor U-Shaped (Ush), and to form a
functional complex with the RUNX transcription factor, Lozenge (Lz). The different isoforms of
Srp and the cooperation between Srp and different cofactors endow srp with pleiotropic
functions during haematopoiesis.
Secondly, we have undertaken an in vivo analysis of the mechanism of segregation of the
two embryonic blood cell lineages. The differentiation of the blood cell progenitors into
plasmatocytes or crystal cells is control by lineage-specific transcription factors. The related
proteins Glial cells missing (Gcm) and Gcm2 control plasmatocyte development, while the
RUNX factor Lozenge (Lz) is specifically required for crystal cell differentiation. We found that
prohemocytes are bipotent progenitors, whose fate is determined by a dynamic interplay
between the lineage-specific transcription factors, Gcm/Gcm2 and Lz. The resolution of blood
cell fate choice corresponds to an original two-steps process in which Gcm/Gcm2 control the
initiation and the maintenance of the crystal cell fate. Interestingly, the transition from a bipotent
haematopoietic precursor to lineage-restricted precursors in Drosophila embryos does not rely
on reciprocal antagonism between two lineage-specific transcription factors, unlike some cel fate decisions in mammalian haematopoeisis
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Submitted on : Thursday, November 2, 2006 - 1:39:24 PM
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Laetitia Bataillé. MECANISMES DE REGULATION
DE L'HEMATOPOÏESE EMBRYONNAIRE
CHEZ LA DROSOPHILE. Biochimie [q-bio.BM]. Université Paul Sabatier - Toulouse III, 2006. Français. ⟨tel-00110898⟩

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