Balancing Germ Cell Renewal and Differentiation
The adult C. elegans gonad contains a population of mitotically proliferating germ cells. As these stem cells divide, a subset of their daughter cells enter meiosis and develop as gametes. This situation is similar to that found in many animal tissues, where a population of stem cells is maintained to allow the continual regeneration of differentiated cells. Mechanisms are typically in place to control the relative proportion of proliferating vs differentiating cells. In the C. elegans germ line, a number of mechanisms regulate the balance between mitotic and meiotic cells. Inductive cell-cell signaling from the somatic gonad to the germ line, mediated via GLP-1/Notch-type signaling, prevents germ cells from entering meiosis. Other factors, such as the translational regulator ATX-2 and nutritional inputs, function in parallel with GLP-1/Notch to promote germline proliferation. Activity of these pathways is counterbalanced by mechanisms to promote meiotic entry. The activity of two translational regulatory pathways, involving activity of the GLD-1 and GLD-2 proteins, is critical for moving germ cells into meiosis.
Our research goal is to understand the mechanisms that regulate the balance between germline proliferation and meiosis. Using genetic approaches, we have identified a number of factors that promote germline proliferation by positively regulating GLP-1/Notch signaling activity or by acting in parallel with GLP-1/Notch signaling. For example, EGO-2 is a positive regulator of GLP-1/Notch and LIN-12/Notch activity in the soma and germ line (Liu and Maine 2007). ATX-2 (ataxin-2 related protein) is a putative translation- and also functions in germline sex determination (Maine et al 2004). The Cyclin E/CDK-2 complex is a positive regulator of germline mitosis (Fox et al 2011). Members of the EGO-1/CSR-1 siRNA pathway (including DRH-3 and EKL-1) also promote germline mitosis in parallel with GLP-1/Notch (Vought et al 2005; She et al 2009).
Selected Related Publications:
Lissemore, J.L., E. Connors, Y. Liu, L. Qiao, B. Yang, M.L. Edgley, S. Flibotte, J. Taylor, V. Au, D.G. Moerman, and E.M. Maine (2018) The molecular chaperone HSP90 promotes Notch signaling in the germline of Caenorhabditis elegans. G3 8:1535-1544.
Safdar, K. , A. Gu, X. Xu, V. Au, J. Taylor, S. Flibotte, D.G. Moerman, and E.M. Maine (2016) UBR-5, a conserved HECT-type E3 ubiquitin ligase, negatively regulates Notch-type signaling in C. elegans. G3 6:2125-2134.
Fox, P.M., V.E. Vought, M. Hanazawa, M-H. Lee, E. M. Maine, and T. Schedl (2011) Cyclin E/CDK-2 regulates proliferative cell fate and cell cycle progression in the C. elegans germline. Development 138, 2223-2234. [Fox_etal_2011]
Liu,Y., and E.M. Maine (2007) The Bro1-domain protein, EGO-2, promotes Notch signaling inCaenorhabditis elegans. Genetics 177, 2265-227. [Liu and Maine 07]
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. [Yu_et_al_06]
Vought, V. E., M. Ohmachi, M-H. Lee, and E.M. Maine (2005) EGO-1, a putative RNA-directed RNA polymerase, promotes germline proliferation in parallel with GLP-1/Notch signaling and regulates the spatial organization of nuclear pore complexes and germline P granules in C. elegans. Genetics 170, 1121-1132. [Vought_etal_05]
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_etal_04_atx2]
Qiao, L., J.L. Lissemore, P. Shu, A. Smardon, M. Gelber, and E.M. Maine (1995) Enhancers of glp-1, a gene required for cell-signaling in C. elegans, define a set of genes required for germline development.Genetics 141, 551-569. [QIAO ETAL_1995]