Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish.
During development, the role of the phosphatidylserine receptor (PSR) in the removal of apoptotic cells that have died is poorly understood. We have investigated this role of PSR in developing zebrafish. Programmed cell death began during the shield stage, with dead cells being engulfed by a neighboring cell that showed a normal-looking nucleus and the nuclear condensation multi-micronuclei of an apoptotic cell. The zebrafish PSR engulfing receptor was cloned (zfpsr), and its nucleotide sequence was compared with corresponding sequences in Drosophila melanogaster (76% identity), human (74%), mouse (72%) and Caenorhabditis elegans (60%). The PSR receptor contained a jmjC domain (residues 143-206) that is a member of the cupin metalloenzyme superfamily, but in this case serves an as yet unknown function(s). psr knockdown by a PSR morpholino oligonucleotide led to accumulation of a large number of dead apoptotic cells in whole early embryo. These cells interfered with embryonic cell migration. In addition, normal development of the somite, brain, heart and notochord was sequentially disrupted up to 24 hours post-fertilization. Development could be rescued in defective embryos by injecting psr mRNA. These results are consistent with a PSR-dependent system in zebrafish embryos that engulfs apoptotic cells mediated by PSR-phagocytes during development, with the system assuming an important role in the normal development of tissues such as the brain, heart, notochord and somite.
Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
Jiann-Ruey
JR
Hong
Gen-Hwa
GH
Lin
Cliff Ji-Fan
CJ
Lin
Wan-Ping
WP
Wang
Chien-Chung
CC
Lee
Tai-Lang
TL
Lin
Jen-Leih
JL
Wu
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D047108:Embryonic Development; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D038081:Organogenesis; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases