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Apoptotic Cell Clearance in Health and Disease

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Front. Immunol. | doi: 10.3389/fimmu.2018.00266

Drosophila GATA factor Serpent establishes phagocytic ability of embryonic macrophages

 Evgeny Shlyakhover1, Boris Shklyar2, Ketty Hakim-Mishnaevski2, Flonia Levy-Adam1 and  Estee Kurant1, 2*
  • 1The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Israel
  • 2Human Biology, University of Haifa, Israel

During Drosophila embryogenesis, a large number of apoptotic cells are efficiently engulfed and degraded by professional phagocytes, macrophages. Phagocytic receptors SIMU, Drpr and 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 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, 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.

Keywords: Drosophila, Macrophages, Phagocytosis, Apoptosis, SIMU, serpent, GATA, development

Received: 11 Sep 2017; Accepted: 30 Jan 2018.

Edited by:

Francesca Granucci, Università degli studi di Milano Bicocca, Italy

Reviewed by:

Alessandra Mancino, San Raffaele Hospital (IRCCS), Italy
Carole Poon, Peter MacCallum Cancer Centre, Australia  

Copyright: © 2018 Shlyakhover, Shklyar, Hakim-Mishnaevski, Levy-Adam and Kurant. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Estee Kurant, University of Haifa, Human Biology, Haifa, Israel, kurantestee@gmail.com