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addition, our data suggest that during embryogenesis, macrophage-mediated clearance of apoptotic cells is not the only - or even the primary - mechanism for the removal of apoptotic cells. In many tissues where programmed cell death occurs as a prominent event during embryogenesis, such as remodeling of the genital ridge during gonad morphogenesis and differentiation of the neural tube, we found almost no co-localization of apoptotic cells and macrophages. This indicates that in these cases clearance of apoptotic cells is directly mediated by neighboring 'bystander' cells rather than by macrophages that have been recruited into areas where apoptosis occurs. Obviously these in vivo clearance mechanisms are not compromised by Ptdsr-deficiency in our knockout mutant. This finding is in line with studies in macrophageless Sfpi1-knockout embryos that are deficient for the hematopoietic-lineage-specific transcription factor PU.1. Here, the phagocytosis of apoptotic cells during embryogenesis is taken over by 'stand-in' mesenchymal neighbors [47]. As recognition of phosphatidylserine is thought to be a universal engulfment mechanism for all cells that are able to phagocytose apoptotic cells, it is very striking that apoptotic cell clearance mediated by non-professional bystander cells is also not compromised by Ptdsr-deficiency."}

{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T12253","span":{"begin":42,"end":55},"obj":"GO:0009790"},{"id":"T12254","span":{"begin":57,"end":67},"obj":"CL:0000235"},{"id":"T12255","span":{"begin":77,"end":105},"obj":"GO:0043277"},{"id":"T12256","span":{"begin":90,"end":105},"obj":"CL:0000445"},{"id":"T12257","span":{"begin":100,"end":105},"obj":"CL_GO_EXT:cell"},{"id":"T12258","span":{"begin":164,"end":190},"obj":"GO:0043277"},{"id":"T12259","span":{"begin":175,"end":190},"obj":"CL:0000445"},{"id":"T12260","span":{"begin":185,"end":190},"obj":"CL_GO_EXT:cell"},{"id":"T12261","span":{"begin":200,"end":207},"obj":"UBERON:0000479"},{"id":"T12262","span":{"begin":214,"end":235},"obj":"GO:0012501"},{"id":"T12263","span":{"begin":225,"end":229},"obj":"CL_GO_EXT:cell"},{"id":"T12264","span":{"begin":271,"end":284},"obj":"GO:0009790"},{"id":"T12265","span":{"begin":312,"end":325},"obj":"UBERON:0005294"},{"id":"T12266","span":{"begin":333,"end":338},"obj":"UBERON:0000991"},{"id":"T12267","span":{"begin":333,"end":352},"obj":"GO:0035262"},{"id":"T12268","span":{"begin":357,"end":372},"obj":"GO_RO_EXT:developmental_differentiation_process"},{"id":"T12269","span":{"begin":380,"end":391},"obj":"UBERON:0001049"},{"id":"T12270","span":{"begin":415,"end":427},"obj":"GO_PATO_EXT:biological_localization_process_or_quality"},{"id":"T12271","span":{"begin":431,"end":440},"obj":"GO_PATO_EXT:apoptotic_process_or_quality"},{"id":"T12272","span":{"begin":431,"end":446},"obj":"CL:0000445"},{"id":"T12273","span":{"begin":441,"end":446},"obj":"CL_GO_EXT:cell"},{"id":"T12274","span":{"begin":451,"end":462},"obj":"CL:0000235"},{"id":"T12275","span":{"begin":499,"end":527},"obj":"GO:0043277"},{"id":"T12276","span":{"begin":512,"end":527},"obj":"CL:0000445"},{"id":"T12277","span":{"begin":522,"end":527},"obj":"CL_GO_EXT:cell"},{"id":"T12278","span":{"begin":576,"end":581},"obj":"CL_GO_EXT:cell"},{"id":"T12279","span":{"begin":597,"end":608},"obj":"CL:0000235"},{"id":"T12280","span":{"begin":624,"end":633},"obj":"GO_EXT:biological_recruitment"},{"id":"T12281","span":{"begin":651,"end":660},"obj":"GO:0006915"},{"id":"T12282","span":{"begin":737,"end":742},"obj":"PR_EXT:000009218"},{"id":"T12283","span":{"begin":770,"end":776},"obj":"SO_EXT:sequence_altered_entity"},{"id":"T12284","span":{"begin":818,"end":828},"obj":"CL:0000235"},{"id":"T12285","span":{"begin":833,"end":838},"obj":"PR_EXT:000001944"},{"id":"T12286","span":{"begin":848,"end":855},"obj":"UBERON:0000922"},{"id":"T12287","span":{"begin":883,"end":896},"obj":"GO:0030097"},{"id":"T12288","span":{"begin":914,"end":927},"obj":"GO_EXT:transcription"},{"id":"T12289","span":{"begin":914,"end":934},"obj":"GO_EXT:transcription_factor"},{"id":"T12290","span":{"begin":935,"end":939},"obj":"PR_EXT:000001944"},{"id":"T12291","span":{"begin":951,"end":982},"obj":"GO:0043277"},{"id":"T12292","span":{"begin":967,"end":982},"obj":"CL:0000445"},{"id":"T12293","span":{"begin":977,"end":982},"obj":"CL_GO_EXT:cell"},{"id":"T12294","span":{"begin":990,"end":1003},"obj":"GO:0009790"},{"id":"T12295","span":{"begin":1032,"end":1043},"obj":"UBERON:0003104"},{"id":"T12296","span":{"begin":1078,"end":1096},"obj":"CHEBI:18303"},{"id":"T12297","span":{"begin":1155,"end":1160},"obj":"CL_GO_EXT:cell"},{"id":"T12298","span":{"begin":1178,"end":1189},"obj":"GO:0006909"},{"id":"T12299","span":{"begin":1190,"end":1199},"obj":"GO_PATO_EXT:apoptotic_process_or_quality"},{"id":"T12300","span":{"begin":1190,"end":1205},"obj":"CL:0000445"},{"id":"T12301","span":{"begin":1200,"end":1205},"obj":"CL_GO_EXT:cell"},{"id":"T12302","span":{"begin":1232,"end":1246},"obj":"CL:0000445"},{"id":"T12303","span":{"begin":1232,"end":1256},"obj":"GO:0043277"},{"id":"T12304","span":{"begin":1242,"end":1246},"obj":"CL_GO_EXT:cell"},{"id":"T12305","span":{"begin":1296,"end":1301},"obj":"CL_GO_EXT:cell"},{"id":"T12306","span":{"begin":1329,"end":1334},"obj":"PR_EXT:000009218"}],"text":"In addition, our data suggest that during embryogenesis, macrophage-mediated clearance of apoptotic cells is not the only - or even the primary - mechanism for the removal of apoptotic cells. In many tissues where programmed cell death occurs as a prominent event during embryogenesis, such as remodeling of the genital ridge during gonad morphogenesis and differentiation of the neural tube, we found almost no co-localization of apoptotic cells and macrophages. This indicates that in these cases clearance of apoptotic cells is directly mediated by neighboring 'bystander' cells rather than by macrophages that have been recruited into areas where apoptosis occurs. Obviously these in vivo clearance mechanisms are not compromised by Ptdsr-deficiency in our knockout mutant. This finding is in line with studies in macrophageless Sfpi1-knockout embryos that are deficient for the hematopoietic-lineage-specific transcription factor PU.1. Here, the phagocytosis of apoptotic cells during embryogenesis is taken over by 'stand-in' mesenchymal neighbors [47]. As recognition of phosphatidylserine is thought to be a universal engulfment mechanism for all cells that are able to phagocytose apoptotic cells, it is very striking that apoptotic cell clearance mediated by non-professional bystander cells is also not compromised by Ptdsr-deficiency."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T12000","span":{"begin":42,"end":55},"obj":"GO:0009790"},{"id":"T12001","span":{"begin":57,"end":67},"obj":"CL:0000235"},{"id":"T12002","span":{"begin":77,"end":105},"obj":"GO:0043277"},{"id":"T12003","span":{"begin":90,"end":105},"obj":"CL:0000445"},{"id":"T12004","span":{"begin":164,"end":190},"obj":"GO:0043277"},{"id":"T12005","span":{"begin":175,"end":190},"obj":"CL:0000445"},{"id":"T12006","span":{"begin":200,"end":207},"obj":"UBERON:0000479"},{"id":"T12007","span":{"begin":214,"end":235},"obj":"GO:0012501"},{"id":"T12008","span":{"begin":271,"end":284},"obj":"GO:0009790"},{"id":"T12009","span":{"begin":312,"end":325},"obj":"UBERON:0005294"},{"id":"T12010","span":{"begin":333,"end":338},"obj":"UBERON:0000991"},{"id":"T12011","span":{"begin":333,"end":352},"obj":"GO:0035262"},{"id":"T12012","span":{"begin":380,"end":391},"obj":"UBERON:0001049"},{"id":"T12013","span":{"begin":431,"end":446},"obj":"CL:0000445"},{"id":"T12014","span":{"begin":451,"end":462},"obj":"CL:0000235"},{"id":"T12015","span":{"begin":499,"end":527},"obj":"GO:0043277"},{"id":"T12016","span":{"begin":512,"end":527},"obj":"CL:0000445"},{"id":"T12017","span":{"begin":597,"end":608},"obj":"CL:0000235"},{"id":"T12018","span":{"begin":651,"end":660},"obj":"GO:0006915"},{"id":"T12019","span":{"begin":737,"end":742},"obj":"PR:000009218"},{"id":"T12020","span":{"begin":818,"end":828},"obj":"CL:0000235"},{"id":"T12021","span":{"begin":833,"end":838},"obj":"PR:000001944"},{"id":"T12022","span":{"begin":848,"end":855},"obj":"UBERON:0000922"},{"id":"T12023","span":{"begin":883,"end":896},"obj":"GO:0030097"},{"id":"T12024","span":{"begin":935,"end":939},"obj":"PR:000001944"},{"id":"T12025","span":{"begin":951,"end":982},"obj":"GO:0043277"},{"id":"T12026","span":{"begin":967,"end":982},"obj":"CL:0000445"},{"id":"T12027","span":{"begin":990,"end":1003},"obj":"GO:0009790"},{"id":"T12028","span":{"begin":1032,"end":1043},"obj":"UBERON:0003104"},{"id":"T12029","span":{"begin":1078,"end":1096},"obj":"CHEBI:18303"},{"id":"T12030","span":{"begin":1178,"end":1189},"obj":"GO:0006909"},{"id":"T12031","span":{"begin":1190,"end":1205},"obj":"CL:0000445"},{"id":"T12032","span":{"begin":1232,"end":1246},"obj":"CL:0000445"},{"id":"T12033","span":{"begin":1232,"end":1256},"obj":"GO:0043277"},{"id":"T12034","span":{"begin":1329,"end":1334},"obj":"PR:000009218"}],"text":"In addition, our data suggest that during embryogenesis, macrophage-mediated clearance of apoptotic cells is not the only - or even the primary - mechanism for the removal of apoptotic cells. In many tissues where programmed cell death occurs as a prominent event during embryogenesis, such as remodeling of the genital ridge during gonad morphogenesis and differentiation of the neural tube, we found almost no co-localization of apoptotic cells and macrophages. This indicates that in these cases clearance of apoptotic cells is directly mediated by neighboring 'bystander' cells rather than by macrophages that have been recruited into areas where apoptosis occurs. Obviously these in vivo clearance mechanisms are not compromised by Ptdsr-deficiency in our knockout mutant. This finding is in line with studies in macrophageless Sfpi1-knockout embryos that are deficient for the hematopoietic-lineage-specific transcription factor PU.1. Here, the phagocytosis of apoptotic cells during embryogenesis is taken over by 'stand-in' mesenchymal neighbors [47]. As recognition of phosphatidylserine is thought to be a universal engulfment mechanism for all cells that are able to phagocytose apoptotic cells, it is very striking that apoptotic cell clearance mediated by non-professional bystander cells is also not compromised by Ptdsr-deficiency."}

{"project":"2_test","denotations":[{"id":"15345036-11076747-55938547","span":{"begin":1055,"end":1057},"obj":"11076747"}],"text":"In addition, our data suggest that during embryogenesis, macrophage-mediated clearance of apoptotic cells is not the only - or even the primary - mechanism for the removal of apoptotic cells. In many tissues where programmed cell death occurs as a prominent event during embryogenesis, such as remodeling of the genital ridge during gonad morphogenesis and differentiation of the neural tube, we found almost no co-localization of apoptotic cells and macrophages. This indicates that in these cases clearance of apoptotic cells is directly mediated by neighboring 'bystander' cells rather than by macrophages that have been recruited into areas where apoptosis occurs. Obviously these in vivo clearance mechanisms are not compromised by Ptdsr-deficiency in our knockout mutant. This finding is in line with studies in macrophageless Sfpi1-knockout embryos that are deficient for the hematopoietic-lineage-specific transcription factor PU.1. Here, the phagocytosis of apoptotic cells during embryogenesis is taken over by 'stand-in' mesenchymal neighbors [47]. As recognition of phosphatidylserine is thought to be a universal engulfment mechanism for all cells that are able to phagocytose apoptotic cells, it is very striking that apoptotic cell clearance mediated by non-professional bystander cells is also not compromised by Ptdsr-deficiency."}