title: Quantitative Differences in a Single Maternal Factor Determine Survival Probabilities among Drosophila Germ Cells.
abstract: Germ cell death occurs in many species [1-3] and has been proposed as a mechanism by which the fittest, strongest, or least damaged germ cells are selected for transmission to the next generation. However, little is known about how the choice is made between germ cell survival and death. Here, we focus on the mechanisms that regulate germ cell survival during embryonic development in Drosophila. We find that the decision to die is a germ cell-intrinsic process linked to quantitative differences in germ plasm inheritance, such that higher germ plasm inheritance correlates with higher primordial germ cell (PGC) survival probability. We demonstrate that the maternal factor lipid phosphate phosphatase Wunen-2 (Wun2) regulates PGC survival in a dose-dependent manner. Since wun2 mRNA levels correlate with the levels of other maternal determinants at the single-cell level, we propose that Wun2 is used as a readout of the overall germ plasm quantity, such that only PGCs with the highest germ plasm quantity survive. Furthermore, we demonstrate that Wun2 and p53, another regulator of PGC survival, have opposite yet independent effects on PGC survival. Since p53 regulates cell death upon DNA damage and various cellular stresses, we hypothesize that together they ensure selection of the PGCs with highest germ plasm quantity and least cellular damage.
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, and Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Maija
authors.initials: M
authors.lastname: Slaidina
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, and Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ruth.lehmann@med.nyu.edu.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D010711:Phosphatidate Phosphatase; C492536:Wun2 protein, Drosophila
keywords: Drosophila; LPP; cell death; cell fate; cell-to-cell variability; germ cells; lipid phosphate phosphatase; nanos; p53; quantitative RNA analysis; wunen