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Transcriptional regulation of hematopoiesis in Drosophila

https://doi.org/10.1016/S1079-9796(03)00028-7Get rights and content

Abstract

As in mammals, blood cells in Drosophila are derived from a common multipotent hematopoietic precursor population. In the embryo, these precursors are derived from the head mesoderm, whereas larval hematopoietic precursors are found in a specialized organ called the lymph gland. This shift in location of hematopoietic differentiation is reminiscent of similar events that occur during mammalian development. Recent analysis has identified several transcriptional regulators in Drosophila that influence hematopoietic lineage commitment. Interestingly, many of these factors are similar to factors directing mammalian hematopoietic differentiation. Although Drosophila blood cells are much less varied in terms of specific lineages, it would appear that many mechanistic aspects by which hematopoietic cell fate is determined have been conserved between Drosophila and mammals. Herein, we describe the Drosophila blood cell types, their physical origin, and the transcriptional regulators that govern this process.

Introduction

Recent investigations have determined that several factors important for hematopoiesis in vertebrates are also functionally conserved in Drosophila. In vertebrate hematopoiesis, a common progenitor cell gives rise to all blood cell lineages [1]. Differentiating progenitors then take on either a lymphoid or myeloid cell fate, which then limits lineage commitment to any fate within a particular subgroup. The lymphoid progenitors give rise to B and T lymphocytes, while myeloid progenitors give rise to many cell types including erythrocytes and monocytes [1]. Although distinct, Drosophila blood cells most closely resemble cells of the vertebrate myeloid lineage, particularly monocyte/macrophages and granulocytes. This distinction is based upon both morphological and functional similarities, including phagocytic and immune-related activities. As will be described further below, Drosophila blood cells are similar to those of vertebrates not only in terms of functionality but also in terms of a genetic hierarchy directing hematopoietic differentiation. This review describes the Drosophila blood cell lineages and what is known about the transcriptional regulators that lead to their specification and differentiation.

Section snippets

Hemocyte cell types

In Drosophila, blood cells are referred to as hemocytes, of which there are at least three terminally differentiated types: plasmatocytes, crystal cells, and lamellocytes. Plasmatocytes are the predominant cell type at all developmental stages and represent approximately 95% of all hemocytes, with crystal cells making up the majority of the remainder [2]. Lamellocytes are produced in very small numbers, if at all, under normal conditions, but can be induced in large numbers under conditions of

Origins of Drosophila hemocytes

In the embryo, both plasmatocytes and crystal cells are derived from a precursor population located in the procephalic mesoderm, first observable in around stage 5 [6], [18]. The hematopoietic precursors (prohemocytes) express the GATA transcription factor Serpent (Srp), which is required for hematopoiesis in Drosophila [18], [19]. As these cells begin to differentiate, plasmatocyte precursors initiate expression of the transcription factor Gcm (glial cells missing) [20] and begin to migrate

Transcriptional regulation during hematopoiesis

The transcription factor Serpent (Srp) is expressed in all hemocyte precursors and is required for hematopoietic development [18], [19]. Serpent is a member (one of five in Drosophila) of the highly conserved GATA family of zinc-finger transcription factors that recognize the consensus DNA binding site WGATAR [24]. All vertebrate GATA factors contain two zinc finger motifs of the Cys-X2-Cys-X17-Cys-X2-Cys type separated by 29 amino acids; the amino-proximal zinc finger is often referred to as

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