Somatic gonad sheath cells and Eph receptor signaling promote germ-cell death in C. elegans.
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ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC3354057 | biostudies-other | 2012 Jun
REPOSITORIES: biostudies-other
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Project description:Somatic gonadal niche cells control the survival, differentiation, and proliferation of germline stem cells. The establishment of this niche-stem cell relationship is critical, and yet the precursors to these two cell types are often born at a distance from one another. The simple Caenorhabditis elegans gonadal primordium, which contains two somatic gonad precursors (SGPs) and two primordial germ cells (PGCs), provides an accessible model for determining how stem cell and niche cell precursors first assemble during development. To visualize the morphogenetic events that lead to formation of the gonadal primordium, we generated transgenic strains to label the cell membranes of the SGPs and PGCs and captured time-lapse movies as the gonadal primordium formed. We identify three distinct phases of SGP behavior: posterior migration along the endoderm towards the PGCs, extension of a single long projection around the adjacent PGC, and a dramatic wrapping over the PGC surfaces. We show that the endoderm and PGCs are dispensable for SGP posterior migration and initiation of projections. However, both tissues are required for the final positioning of the SGPs and the morphology of their projections, and PGCs are absolutely required for SGP wrapping behaviors. Finally, we demonstrate that the basement membrane component laminin, which localizes adjacent to the developing gonadal primordium, is required to prevent the SGPs from over-extending past the PGCs. Our findings provide a foundation for understanding the cellular and molecular regulation of the establishment of a niche-stem cell relationship.
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Project description:The myoepithelial sheath in the somatic gonad of the nematode Caenorhabditis elegans has nonstriated contractile actomyosin networks that produce highly coordinated contractility for ovulation of mature oocytes. Two myosin heavy chains are expressed in the myoepithelial sheath, which are also expressed in the body-wall striated muscle. The troponin/tropomyosin system is also present and essential for ovulation. Therefore, although the myoepithelial sheath has smooth muscle-like contractile apparatuses, it has a striated muscle-like regulatory mechanism through troponin/tropomyosin. Here we report that the myoepithelial sheath has a distinct myosin population containing nonmuscle myosin II isoforms, which is regulated by phosphorylation and essential for ovulation. MLC-4, a nonmuscle myosin regulatory light chain, localizes to small punctate structures and does not colocalize with large, needle-like myosin filaments containing MYO-3, a striated-muscle myosin isoform. RNA interference of MLC-4, as well as of its upstream regulators, LET-502 (Rho-associated coiled-coil forming kinase) and MEL-11 (a myosin-binding subunit of myosin phosphatase), impairs ovulation. Expression of a phosphomimetic MLC-4 mutant mimicking a constitutively active state also impairs ovulation. A striated-muscle myosin (UNC-54) appears to provide partially compensatory contractility. Thus the results indicate that the two spatially distinct myosin II populations coordinately regulate ovulatory contraction of the myoepithelial sheath.
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Project description:MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in animal development and physiology, though functions for most miRNAs remain unknown. Worms with reduced miRNA biogenesis due to loss of Drosha or Pasha/DGCR8 activity are sterile and fail to ovulate, indicating that miRNAs are required for the process of oocyte maturation and ovulation. Starting with this penetrant sterile phenotype and using new strains created to perform tissue specific RNAi, we characterized the roles of the C. elegans Pasha, pash-1, and two miRNA-specific Argonautes, alg-1 and alg-2, in somatic gonad cells and in germ cells in the regulation of ovulation. Conditional loss of pash-1 activity resulted in a reduced rate of ovulation and in basal and ovulatory sheath contractions. Similarly, knockdown of miRNA-specific Argonautes in the cells of the somatic gonad by tissue-specific RNAi results in a reduction of the ovulation rate and in basal and ovulatory sheath contractions. Reduced miRNA pathway gene activity resulted in a range of defects, including oocytes that were pinched upon entry of the oocyte into the distal end of the spermatheca in about 42% of the ovulation events observed following alg-1 RNAi. This phenotype was not observed on worms exposed to control RNAi. In contrast, knockdown of alg-1 and alg-2 in germ cells results in few defects in oocyte maturation and ovulation. These data identify specific steps in the process of ovulation that require miRNA pathway gene activity in the somatic gonad cells.
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Project description:C. elegans larvae integrate environmental information and developmental decisions [1-3]. In favorable conditions, worms develop rapidly and continuously through four larval stages into reproductive adulthood. However, if conditions are unfavorable through the second larval stage, worms enter dauer diapause, a state of global and reversible developmental arrest in which precursor cells remain quiescent and preserve developmental potential, anticipating developmental progression if conditions improve. Signaling from neurons, hypodermis, and intestine regulate the appearance and behavior of dauer larvae and many aspects of developmental arrest of the non-gonadal soma [1, 4, 5]. Here, we show that the decision of somatic gonad blast cells (SGBs) and germline stem cells (GSCs) to be quiescent or progress developmentally is regulated differently from the non-gonadal soma: daf-18/PTEN acts non-autonomously within the somatic gonad to maintain developmental quiescence of both SGBs and GSCs. Our analysis suggests that daf-18 acts in somatic gonad cells to produce a "pro-quiescence" signal (or signals) that acts inter se and between the somatic gonad and the germline. The inferred signal does not require DAF-2/insulin receptor or maintain quiescence of the nearby sex myoblasts, and developmental progression in daf-18(0) does not require dafachronic acids. Abrogating quiescence in dauer results in post-dauer sterility. Our results implicate the somatic gonad as an endocrine organ to synchronize somatic gonad and germline development during dauer diapause and recovery, and our finding that PTEN acts non-autonomously to control blast cell quiescence may be relevant to its function as a tumor suppressor in mammals and to combating parasitic nematodes.
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Project description:In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12.
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Project description:The Caenorhabditis elegans somatic gonadal precursors (SGPs) are multipotent progenitors that give rise to all somatic tissues of the adult reproductive system. The hunchback and Ikaros-like gene ehn-3 is expressed specifically in SGPs and is required for their development into differentiated tissues of the somatic gonad. To find novel genes involved in SGP development, we used a weak allele of ehn-3 as the basis for a reverse genetic screen. Feeding RNAi was used to screen ?2400 clones consisting of transcription factors, signaling components, and chromatin factors. The screen identified five members of the C. elegans SWI/SNF chromatin remodeling complex as genetic enhancers of ehn-3. We characterized alleles of 10 SWI/SNF genes and found that SWI/SNF subunits are required for viability and gonadogenesis. Two conserved SWI/SNF complexes, PBAF and BAF, are defined by their unique array of accessory subunits around a common enzymatic core that includes a catalytic Swi2/Snf2-type ATPase. Tissue-specific RNAi experiments suggest that C. elegans PBAF and BAF complexes control different processes during somatic gonadal development: PBRM-1, a signature subunit of PBAF, is important for normal SGP development, whereas LET-526, the distinguishing subunit of BAF, is required for development of a differentiated cell type, the distal tip cell (DTC). We found that the SWSN-4 ATPase subunit is required for SGP and DTC development. Finally, we provide evidence that C. elegans PBAF subunits and hnd-1/dHand are important for the cell fate decision between SGPs and their differentiated sisters, the head mesodermal cells.
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