Somatic gonad sheath cells and Eph receptor signaling promote germ-cell death in C. elegans

In C. elegans, gap junctions couple cells of the somatic gonad with the germline to support germ cell proliferation and gametogenesis. We previously characterized a strong loss-of-function mutation (T239I) affecting the second extracellular loop (EL2) of the somatic INX-8 hemichannel subunit. These mutant hemichannels form non-functional gap junctions with germline-expressed innexins. Here we describe the characterization of mutations that restore germ cell proliferation in the T239I EL2 mutant background. We recovered seven intragenic mutations located in diverse domains of INX-8 but not the EL domains. These second-site mutations compensate for the original channel defect to varying degrees, from nearly complete wild-type rescue, to partial rescue of germline proliferation. One suppressor mutation (E350K) supports the innexin cryo-EM structural model that the channel pore opening is surrounded by a cytoplasmic dome. Two suppressor mutations (S9L and I36N) may form leaky hemichannels that support germline proliferation but cause the demise of somatic sheath cells. Phenotypic analyses of three other suppressors reveal an equivalency in the rescue of germline proliferation and comparable delays in gametogenesis but a graded rescue of fertility. These latter mutations may be useful to probe interactions with the biochemical pathways that produce the molecules transiting through soma-germline gap junctions.

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Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽

10.1242/dev.126.5.1011 ◽

1999 ◽

Vol 126 (5) ◽

pp. 1011-1022 ◽

Cited By ~ 8

Author(s):

T.L. Gumienny ◽

E. Lambie ◽

E. Hartwieg ◽

H.R. Horvitz ◽

M.O. Hengartner

Keyword(s):

Cell Death ◽

Caenorhabditis Elegans ◽

Germ Cell ◽

Somatic Cell ◽

Cell Fate ◽

Germ Cells ◽

Mapk Pathway ◽

Apoptotic Cell ◽

C Elegans ◽

Pathway Activation

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.

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Stem cell niche exit in C. elegans via orientation and segregation of daughter cells by a cryptic cell outside the niche

eLife ◽

10.7554/elife.56383 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 3

Author(s):

Kacy L Gordon ◽

Jay W Zussman ◽

Xin Li ◽

Camille Miller ◽

David R Sherwood

Keyword(s):

Stem Cell ◽

Germ Cell ◽

Stem Cell Niche ◽

Cell Pair ◽

C Elegans ◽

Daughter Cells ◽

Somatic Gonad ◽

Cell Niche ◽

Disproportionate Number ◽

Gonad Cell

Stem cells reside in and rely upon their niche to maintain stemness but must balance self-renewal with the production of daughters that leave the niche to differentiate. We discovered a mechanism of stem cell niche exit in the canonical C. elegans distal tip cell (DTC) germ stem cell niche mediated by previously unobserved, thin, membranous protrusions of the adjacent somatic gonad cell pair (Sh1). A disproportionate number of germ cell divisions were observed at the DTC-Sh1 interface. Stem-like and differentiating cell fates segregated across this boundary. Spindles polarized, pairs of daughter cells oriented between the DTC and Sh1, and Sh1 grew over the Sh1-facing daughter. Impeding Sh1 growth by RNAi to cofilin and Arp2/3 perturbed the DTC-Sh1 interface, reduced germ cell proliferation, and shifted a differentiation marker. Because Sh1 membrane protrusions eluded detection for decades, it is possible that similar structures actively regulate niche exit in other systems.

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Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans

Scientific Reports ◽

10.1038/srep15417 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 13

Author(s):

Marshall Deline ◽

Julia Keller ◽

Michael Rothe ◽

Wolf-Hagen Schunck ◽

Ralph Menzel ◽

...

Keyword(s):

Cell Death ◽

Germ Cell ◽

Linolenic Acid ◽

Gamma Linolenic Acid ◽

C Elegans

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Identification of X-Linked Genes Required for Migration and Programmed Cell Death of Drosophila melanogaster Germ Cells

Genetics ◽

10.1093/genetics/162.1.273 ◽

2002 ◽

Vol 162 (1) ◽

pp. 273-284 ◽

Cited By ~ 1

Author(s):

Clark R Coffman ◽

Rachel C Strohm ◽

Fredrick D Oakley ◽

Yukiko Yamada ◽

Danielle Przychodzin ◽

...

Keyword(s):

Cell Death ◽

Cell Migration ◽

Germ Cell ◽

Germ Cells ◽

Posterior Pole ◽

Developmentally Regulated ◽

Regulated Cell Death ◽

Somatic Gonad ◽

Programmed Death ◽

Germ Cell Migration

Abstract Drosophila germ cells form at the posterior pole of the embryo and migrate to the somatic gonad. Approximately 50% of the germ cells that form reach their target. The errant cells within the embryo undergo developmentally regulated cell death. Prior studies have identified some autosomal genes that regulate germ cell migration, but the genes that control germ cell death are not known. To identify X-linked genes required for germ cell migration and/or death, we performed a screen for mutations that disrupt these processes. Here we report the identification of scattershot and outsiders, two genes that regulate the programmed death of germ cells. The scattershot gene is defined by a mutation that disrupts both germ cell migration and the death of germ cells ectopic to the gonad. Maternal and zygotic expression of scattershot is required, but the migration and cell death functions can be genetically uncoupled. Zygotic expression of wild-type scattershot rescues germ cell pathfinding, but does not restore the programmed death of errant cells. The outsiders gene is required zygotically. In outsiders mutant embryos, the appropriate number of germ cells is incorporated into the gonad, but germ cells ectopic to the gonad persist.

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The C. elegans gonadal sheath Sh1 cells associate selectively with a differentiating germ cell population in the proliferative zone

10.1101/2021.11.08.467787 ◽

2021 ◽

Author(s):

Xin Li ◽

Noor Singh ◽

Camille Miller ◽

India Washington ◽

Bintou Sosseh ◽

...

Keyword(s):

Germ Cell ◽

Germ Cells ◽

Germ Line ◽

Fluorescent Proteins ◽

Temperature Sensitive ◽

Variable Expression ◽

C Elegans ◽

Proliferative Zone ◽

Adult Hermaphrodite ◽

Sheath Cells

The C. elegans adult hermaphrodite germ line is surrounded by a thin tube formed by somatic sheath cells that support germ cells as they mature from the stem-like mitotic state through meiosis, gametogenesis and ovulation. Recently, we discovered that the distal-most Sh1 sheath cells associate with mitotic germ cells as they exit the niche. Here we report that these distal sheath-associated germ cells differentiate first in animals with temperature-sensitive mutations affecting germ cell state, and stem-like germ cells are maintained distal to the Sh1 boundary. We analyze several markers of the distal sheath, which is best visualized with endogenously tagged membrane proteins, as overexpressed fluorescent proteins fail to localize to distal membrane processes and can cause gonad morphology defects. However, such reagents with highly variable expression can be used to determine the relative positions of the two Sh1 cells, one of which often extends further distal than the other.

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