A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans.
Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes. The molecular mechanisms controlling the decision between self-renewal and differentiation are central unsolved problems in developmental biology with potentially broad medical implications. In Caenorhabditis elegans, germline stem cells are controlled by the somatic distal tip cell. FBF-1 and FBF-2, two nearly identical proteins, which together are called FBF ('fem-3 mRNA binding factor'), were originally discovered as regulators of germline sex determination. Here we report that FBF also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline proliferation is initially normal, but stem cells are not maintained. We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle. FBF belongs to the PUF family ('Pumilio and FBF') of RNA-binding proteins. Pumilio controls germline stem cells in Drosophila females, and, in lower eukaryotes, PUF proteins promote continued mitoses. We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells.
Crittenden
Sarah L
SL
Howard Hughes Medical Institute, University of Wisconsin Madison, Madison, Wisconsin 53706, USA.
Bernstein
David S
DS
Bachorik
Jennifer L
JL
Thompson
Beth E
BE
Gallegos
Maria
M
Petcherski
Andrei G
AG
Moulder
Gary
G
Barstead
Robert
R
Wickens
Marvin
M
Kimble
Judith
J
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D017124:Conserved Sequence; D012734:Disorders of Sex Development / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005786:Gene Expression Regulation; D017238:Genes, Helminth / Q000235:genetics; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C109286:fem-3-binding protein, C elegans