Maintaining the balance between proliferation and meiotic entry
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Wildtype adult hermaphrodite contains proliferating germ cells at the distal end of the gonad (*) and gametes (sperm and oocytes) at the proximal end. In the absence of GLP-1/ Notch signaling, germ cells are depleted and the hermaphrodite is sterile.
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In the C. elegans germ line, the balance between proliferationand meiosis is tightly regulated to ensure the continued formation of gametes throughout adulthood. A similar phenomenon occurs in many animal tissues, where a population of proliferating (stem) cells allows the continual regeneration of differentiated cells. In the C. elegans germ line, proliferation is maintained by inductive signals from the somatic gonad mediated by GLP-1/Notch. One effect of GLP-1/Notch signaling is to prevent germ cells from exiting mitosis, entering meiosis, and differentiating. The effect is balanced in adult animals by the activities of the GLD-1 and GLD-2 pathways, which act together to trigger meiotic entry.
Our research goals are to understand processes that promote germline proliferation and to identify factors that interact with the GLD-1 and GLD-2 pathways to promote entry of germ cells into meiosis. We initially used genetic screens to identify mutations that either enhance or suppress the germline proliferation defect caused by reduced GLP-1/Notch signaling. We expect that the wildtype functions of these genes are to positively regulate germline proliferation or positively regulate meiotic entry, respectively. For example, we identified ATX-2 (ataxin-2 related protein) as a positive regulator of germ cell proliferation that acts in parallel with GLP-1/Notch signaling (Maine et al. 2004).
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Proliferating germ cells (green) are present only at the distal (left) end of the wildtype (A) and atx-2 deficient (B) germ line. Most germ cells are meiotic (orange). In contrast, proliferating cells are found throughout the gld-2 gld-1 double mutant germ line (C). (D) Reduced atx-2 activity compensates for the loss of gld-2 gld-1 function: most of the germ line is meiotic. Images from Maine et al. 2004 well as on the X.
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Genetic data suggest that ATX-2 expression may be regulated by GLD-1 and GLD-2 pathways, or indeed ATX-2 may co-regulate some targets of GLD-1 and GLD-2. ATX-2 also functions in sex determination, promoting the oocyte fate. Identification and analysis of other positive regulators of germline proliferation is underway.
In other work, we identified the sog genes as negative regulators of germ cell proliferation, acting in opposition to the GLP-1/Notch signaling pathway (Maine & Kimble 1993; A. Smardon & E. Maine, unpublished data). We hypothesize that SOG proteins promote the entry of germ cells into meiosis. Some sog genes also function in sex determination. We are collaborating with Tim Schedl (Washington University) to initiate molecular analysis of the sog genes.
Selected Related Publications:
Yu, X., V. E. Vought, B. Conradt, and E.M. Maine (2006) Eukaryotic translation factors 5B activity regulates larval growth rate and germline development in Caenorhabditis elegans. Genesis 44, 412-418.
Maine, E.M. D. Hansen, D. Springer, and V. E. Vought (2004) C. elegans atx-2 promotes germline proliferation and the oocyte fate. Genetics 168, 817-830.
Maine,E.M., and J. Kimble (1993) Suppressors of glp-1, a gene required for cell communication during development in Caenorhabditis elegans, define a set of interacting genes. Genetics 135, 1011-1022.
For more details about my other research and related publications, please select from the following:
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