Abstract
During Drosophila embryogenesis, a large number of apoptotic cells are efficiently engulfed and degraded by professional phagocytes, macrophages. Phagocytic receptors Six-Microns-Under (SIMU), Draper (Drpr) and Croquemort (Crq) are specifically expressed in embryonic macrophages and required for their phagocytic function. However, how this function is established during development remains unclear. Here we demonstrate that the key regulator of Drosophila embryonic hemocyte differentiation, the transcription factor Serpent (Srp), plays a central role in establishing macrophage phagocytic competence. Srp, a homolog of the mammalian GATA factors, is required and sufficient for the specific expression of SIMU, Drpr and Crq receptors in embryonic macrophages. Moreover, we show that each of these receptors can significantly rescue phagocytosis defects of macrophages in srp mutants, including their distribution in the embryo and engulfment of apoptotic cells. This reveals that the proficiency of macrophages to remove apoptotic cells relies on the expression of SIMU, Crq and/or Drpr. However, Glial Cells Missing (GCM) acting downstream of Srp in the differentiation of hemocytes, is dispensable for their phagocytic function during embryogenesis. Taken together, our study discloses the molecular mechanism underlying the development of macrophages as skilled phagocytes of apoptotic cells.
Highlights
During normal development of multicellular organisms superfluous cells are eliminated through apoptosis and subsequent phagocytosis by “professional” phagocytes, macrophages and immature dendritic cells, and “non-professional” tissue-resident neighboring cells [1,2,3]
We found that expression of each phagocytic receptor, SIMU, Drpr or Crq, alone in srp mutant macrophages is sufficient to partially rescue their phagocytic skills and distribution, revealing the crucial role each receptor plays in establishment of cell phagocytic ability
Apoptotic cell clearance by “professional” and “non-professional” phagocytes plays a critical role during development of multicellular organisms
Summary
During normal development of multicellular organisms superfluous cells are eliminated through apoptosis and subsequent phagocytosis by “professional” phagocytes, macrophages and immature dendritic cells, and “non-professional” tissue-resident neighboring cells [1,2,3]. Drosophila “professional” phagocytes macrophages (plasmatocytes) are the most abundant cells in Drosophila hemolymph (~95%), which to mammalian macrophages are responsible for Serpent Regulates Phagocytosis by Macrophages phagocytosis of apoptotic cells, microbes and tissue remodeling [11,12,13,14,15]. They originate from the cephalic mesoderm in the embryo and remain in circulation throughout all stages of development [12, 16]. How the expression of SIMU and Drpr is regulated in macrophages remains unknown
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