First published online as a Review in Advance on June 22, 2007

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Stem Cells

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

Judith Kimble and Sarah L. Crittenden

Department of Biochemistry and Howard Hughes Medical Institute, University of Wisconsin, Madison, Wisconsin 53706-1544; email: jekimble@wisc.edu, slcritte@wisc.edu

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.

Acronyms and Definitions

Actual germline stem cell: a cell that actually accomplishes both self-renewal and the generation of differentiated cells

Asymmetric division: the generation of daughters with distinct fates

CPEB: cytoplasmic polyadenylation element binding protein

DTC: distal tip cell

FBF-1 and FBF-2 (collectively called FBF): PUF RNA-binding proteins that control GSC maintenance and germline sex determination

FOG-1: CPEB-related RNA-binding protein critical for germline proliferation and sperm specification

FOG-3: a Tob/Btg-related protein critical for germline proliferation and sperm specification

Germ line: cells dedicated to the production of gametes

GLD-1: STAR/quaking RNA-binding protein and translational repressor

GLD-2: cytoplasmic poly(A) polymerase and translational activator

GLD-3: Bicaudal-C homolog that antagonizes FBF and enhances GLD-2

GLP-1: one of two C. elegans Notch receptors

GSC reservoir: cells that are capable of self-renewal but that instead normally differentiate

GSC: germline stem cell

Hermaphrodite: in C. elegans, a modified female that produces

70 primary spermatocytes and then switches to make oocytes continuously. Oocytes can be fertilized by the hermaphrodite's own sperm (self-fertilization) or by sperm from a male (cross-fertilization)

LAG-2: Delta homolog and ligand for the GLP-1/Notch receptor

Niche: a microenvironment that is essential for stem cell maintenance

NOS-3: RNA regulator related to Drosophila Nanos that can act with PUF proteins

Notch signaling: a signal transduction pathway that controls proliferation and differentiation throughout the animal kingdom. Core components of this pathway (e.g., GLP-1, LIN-12) have been conserved from worms to humans

PUF proteins: conserved family of RNA-binding proteins that control gene expression by regulating mRNA translation or stability

Self-renewal: the process by which a stem cell makes more stem cells

Stem cell: a cell that is capable of generating both additional stem cells and differentiated cells

Totipotency: having the potential to generate all differentiated cell types

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