Controls of Germline Stem Cells, Entry into Meiosis, and the Sperm/Oocyte Decision inCaenorhabditis elegans

Abstract

The Caenorhabditis elegans germ line provides an exceptional model for analysis of the molecular controls governing stem cell maintenance, the cell cycle transition from mitosis to meiosis, and the choice of sexual identity-sperm or oocyte. Germline stem cells are maintained in an undifferentiated state within a well-defined niche formed by a single somatic cell, the distal tip cell (DTC). In both sexes, the DTC employs GLP-1/Notch signaling and FBF/PUF RNA-binding proteins to maintain stem cells and promote mitotic divisions, three additional RNA regulators (GLD-1/quaking, GLD-2/poly(A) polymerase, and GLD-3/Bicaudal-C) control entry into meiosis, and FOG-1/CPEB and FOG-3/Tob proteins govern sperm specification. These key regulators are part of a robust regulatory network that controls germ cell proliferation, stem cell maintenance, and sex determination. Parallels with controls in other organisms include the use of PUF proteins for stem cell maintenance and the prominence of mRNA regulation for the control of germline development.

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

“…In adults, all germ cell stages from mitotic proliferation through meiotic prophase and gametogenesis are present in a linear array (Hansen and Schedl, 2006;Kimble and Crittenden, 2007). Germ cells divide mitotically in the distal-most part of the germline, termed the proliferative or mitotic zone (Fig.…”

More complicated than it looks: assembly of Notch pathway transcription complexes

“…Notch signaling occurs between adjacent cells often resulting in the specification of different cell types from equivalent progenitor cells (Tanigaki and Honjo, 2007). In addition to differentiation, Notch also has important roles in cellular proliferation, hypoxia, apoptosis and establishing the stem-cell niche (Kimble and Crittenden, 2007;Ruas et al, 2007). The Notch pathway is regulated at multiple levels-outside of the cell, in the cytoplasm and within the nucleus-the importance of which is emphasized by the prevalence of misregulated Notch signaling and its intimate association with human disease.…”

Genetics of germ cell development

“…FOG-1, a cytoplasmic poly-A element binding (CPEB) protein, and FOG-3, a Tob/BTG transcriptional/translational regulator, promote SPERMATOGENESIS; they are inhibited by the FBF proteins and by TRA-1, a conserved transcription factor that promotes female/hermaphrodite specification in somatic tissues (reviewed in refs 62 and 63). [62][63][64][65][66][67][68] TRA-1 is inhibited by FEM-3, which acts along with the additional factors FEM-1 and FEM-2 to push the germ cells toward continued spermatogenesis. 69,70 FEM-3 is opposed by the RNA-binding protein DAZ-1, which promotes the switch to OOGENESIS.…”