Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo.
Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo.
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Apoptosis and the subsequent clearance of these dying cells occur throughout development and adult life in many tissues. Failure to promptly clear apoptotic cells has been linked to many diseases. ELMO1 is an evolutionarily conserved cytoplasmic engulfment protein that functions downstream of the phosphatidylserine receptor BAI1, and, along with Dock180 and Rac1, promotes internalization of the dying cells. Here, we generated ELMO1-deficient mice, and unexpectedly found them to be viable and grossly normal. However, ELMO1-deficient mice had a striking testicular pathology, with disrupted seminiferous epithelium, multi-nucleated giant cells, uncleared apoptotic germ cells, and decreased sperm output. Subsequent in vitro and in vivo analyses revealed a crucial role for ELMO1 in the phagocytic clearance of apoptotic germ cells by Sertoli cells lining the seminiferous epithelium. The engulfment receptor BAI1 and the GTPase Rac (upstream and downstream of ELMO1, respectively) were also important for Sertoli cell-mediated engulfment. Collectively, these findings uncover a selective requirement for ELMO1 in Sertoli cell-mediated removal of apoptotic germ cells and make a compelling case for a relationship between engulfment and tissue homeostasis in vivo.
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