Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.
Reference
Reference
Abrams
J. M.
, White
K.
, Fessler
L. I.
, Steller
H.
(1993
) Programmed cell death during Drosophila embryogenesis.
Development
117
, 29
–43
Adams
J. M.
, Cory
S.
(1998
) The Bcl-2 protein family: arbiters of cell survival.
Science
281
, 1322
–1326
Brenner
S.
(1974
) The genetics of Caenorhabditis elegans.
Genetics
77
, 71
–94
Chang
B. S.
, Minn
A. J.
, Muchmore
S. W.
, Fesik
S. W.
, Thompson
C. B.
(1997
) Identification of a novel regulatory domain in Bcl-X(L) and Bcl-2.
EMBO J
16
, 968
–977
Chao
D. T.
, Korsmeyer
S. J.
(1998
) BCL-2 family: regulators of cell death.
Annu. Rev. Immunol
16
, 395
–419
Church
D. L.
, Guan
K. L.
, Lambie
E. J.
(1995
) Three genes of the MAP kinase cascade, mek-2, mpk-1/sur-1 and let-60 ras, are required for meiotic cell cycle progression in Caenorhabditis elegans.
Development
121
, 2525
–2535
Conradt
B.
, Horvitz
H. R.
(1998
) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9.
Cell
93
, 519
–529
Datta
R.
, Manome
Y.
, Taneja
N.
, Boise
L. H.
, Weichselbaum
R.
, Thompson
C. B.
, Slapak
C. A.
, Kufe
D.
(1995
) Overexpression of Bcl-XL by cytotoxic drug exposure confers resistance to ionizing radiation-induced internucleosomal DNA fragmentation.
Cell Growth Differ
6
, 363
–370
del Peso
L.
, Gonzalez-Garcia
M.
, Page
C.
, Herrera
R.
, Nunez
G.
(1997
) Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.
Science
278
, 687
–689
Driscoll
M.
(1992
) Molecular genetics of cell death in the nematode Caenorhabditis elegans.
J. Neurobiol
23
, 1327
–1351
Ellis
H. M.
, Horvitz
H. R.
(1986
) Genetic control of programmed cell death in the nematode C. elegans.
Cell
44
, 817
–829
Ellis
R. E.
, Horvitz
H. R.
(1991
) Two C. elegans genes control the programmed deaths of specific cells in the pharynx.
Development
112
, 591
–603
Ellis
R. E.
, Jacobson
D. M.
, Horvitz
H. R.
(1991
) Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans.
Genetics
129
, 79
–94
Ellis
R. E.
, Yuan
J. Y.
, Horvitz
H. R.
(1991
) Mechanisms and functions of cell death.
Annu. Rev. Cell Biol
7
, 663
–698
Francis
R.
, Barton
M. K.
, Kimble
J.
, Schedl
T.
(1995
) gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans.
Genetics
139
, 579
–606
Gibert
M. A.
, Starck
J.
, Beguet
B.
(1984
) Role of the gonad cytoplasmic core during oogenesis of the nematode Caenorhabditis elegans.
Biol. Cell
50
, 77
–85
Hedgecock
E. M.
, Sulston
J. E.
, Thomson
J. N.
(1983
) Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans.
Science
220
, 1277
–1279
Hengartner
M. O.
, Ellis
R. E.
, Horvitz
H. R.
(1992
) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death.
Nature
356
, 494
–499
Hengartner
M. O.
, Horvitz
H. R.
(1994
) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2.
Cell
76
, 665
–676
Hengartner
M. O.
, Horvitz
H. R.
(1994
) The ins and outs of programmed cell death during C. elegans development.
Philos. Trans. R. Soc. Lond. B. Biol. Sci
345
, 243
–246
Hengartner
M. O.
(1997
) Apoptosis. CED-4 is a stranger no more.
Nature
388
, 714
–715
Hengartner
M. O.
(1998
) Apoptosis. Death cycle and Swiss army knives.
Nature
391
, 441
–442
Hodgkin
J. A.
, Brenner
S.
(1977
) Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans.
Genetics
86
, 275
–287
Hodgkin
J.
(1980
) More sex-determination mutants of Caenorhabditis elegans.
Genetics
96
, 649
–664
Horvitz
H. R.
, Shaham
S.
, Hengartner
M. O.
(1994
) The genetics of programmed cell death in the nematode Caenorhabditis elegans.
Cold Spring Harb. Symp. Quant. Biol
59
, 377
–385
Kayne
P.
, Sternberg
P.
(1995
) Ras pathways in Caenorhabditis elegans.
Curr. Opin. Genet. Dev
5
, 38
–43
Kerr
J. F.
, Wyllie
A. H.
, Currie
A. R.
(1972
) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
Br. J. Cancer
26
, 239
–257
Kimble
J.
, Hirsh
D.
(1979
) The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans.
Dev. Biol
70
, 396
–417
MacLennan
I.
(1994
) Germinal centers.
Annu. Rev. Immunol
12
, 117
–139
Reed
J. C.
(1994
) Bcl-2 and the regulation of programmed cell death.
J. Cell Biol
124
, 1
–6
Robey
E.
, Fowlkes
B.
(1994
) Selective events in T cell development.
Annu. Rev. Immunol
12
, 675
–705
Starck
J.
(1977
) Radioautographic Study of RNA Synthesis in Caenorhabditis elegans (Bergerac Variety) Oogenesis.
Biol. Cellulaire
30
, 181
–182
Sternberg
P. W.
, Horvitz
H. R.
(1981
) Gonadal cell lineages of the nematode Panagrellus redivivus and implications for evolution by the modification of cell lineage.
Dev. Biol
88
, 147
–166
Sulston
J. E.
, Brenner
S.
(1974
) The DNA of Caenorhabditis elegans.
Genetics
77
, 95
–104
Sulston
J. E.
, Horvitz
H. R.
(1977
) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans.
Dev. Biol
56
, 110
–156
Sulston
J. E.
, Albertson
D. G.
, Thomson
J. N.
(1980
) The Caenorhabditis elegans male: postembryonic development of nongonadal structures.
Dev. Biol
78
, 542
–576
Sulston
J. E.
, Schierenberg
E.
, White
J. G.
, Thomson
J. N.
(1983
) The embryonic cell lineage of the nematode Caenorhabditis elegans.
Dev. Biol
100
, 64
–119
Wang
H. G.
, Rapp
U. R.
, Reed
J. C.
(1996
) Bcl-2 targets the protein kinase Raf-1 to mitochondria.
Cell
87
, 629
–638
White
K.
, Grether
M. E.
, Abrams
J. M.
, Young
L.
, Farrell
K.
, Steller
H.
(1994
) Genetic control of programmed cell death in Drosophila.
Science
264
, 677
–683
Wyllie
A. H.
, Kerr
J. F. R.
, Currie
A. R.
(1980
) Cell death: the significance of apoptosis.
Int. Rev. Cytol
68
, 251
–306
Xue
D.
, Shaham
S.
, Horvitz
H. R.
(1996
) The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease.
Genes Dev
10
, 1073
–1083
Yang
E.
, Zha
J.
, Jockel
J.
, Boise
L. H.
, Thompson
C. B.
, Korsmeyer
S. J.
(1995
) Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death.
Cell
80
, 285
–291
Yin
X. M.
, Oltvai
Z. N.
, Veis-Novack
D. J.
, Linette
G. P.
, Korsmeyer
S. J.
(1994
) Bcl-2 gene family and the regulation of programmed cell death.
Cold Spring Harb. Symp. Quant. Biol
59
, 387
–393
Yuan
J.
, Horvitz
H. R.
(1992
) The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death.
Development
116
, 309
–320
Yuan
J.
, Shaham
S.
, Ledoux
S.
, Ellis
H. M.
, Horvitz
H. R.
(1993
) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.
Cell
75
, 641
–652
Zou
H.
, Henzel
W. J.
, Liu
X.
, Lutschg
A.
, Wang
X.
(1997
) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3.
Cell
90
, 405
–413
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