Although a role of the molecular chaperone Hsp90 in germ cells has been predicted from its expression pattern, its cellular function remains unknown. Our previous reports have shown that DAF-21/Hsp90 is predominantly expressed in germ cells throughout the C. elegans life cycle(1). To clarify the role of
daf-21 in germline development, we searched for germline-related phenotypes based on RNAi strategy against the
daf-21 locus. We found two apparent germline defect phenotypes in
daf-21 (RNAi) F0 animals and examined the basis for each phenotype. First, in
daf-21 mutants, mitotically dividing germline stem cells were arrested at the most distal end of the gonad arms. This mitosis arrest phenotype appeared very similar to that observed with
cdk-1 (RNAi) phenocopies, wherein
cdk-1 is a C. elegans homolog of Cdc2, known as a key regulator of cell cycle machinery. Moreover, CDK-1, which is cytoplasmically expressed in the distal gonad region of wild-type animals, was significantly decreased in
daf-21 (RNAi). This result suggests that DAF-21 is required for expression, proper folding, or stability of CDK-1. Second, the loss of
daf-21 function in
daf-21 (RNAi) led to defective diakinesis arrest oocytes (Dda phenotype), as judged by the premature segregation of chromosomes. The Dda phenotype of
daf-21 (RNAi) was suppressed in
cdk-1 (RNAi), whereas it was not in
cdc-25 (RNAi). (CDC-25 is known to positively regulate CDK-1 (i.e., Cdc2 homolog) by removing the inhibitory phosphates on CDK-1.) This result is consistent with the idea that the phenotype depends on the CDK-1 activity and that the inhibitory phosphates on CDK-1 are absent in the
daf-21 loss of function background. The idea is further supported by our finding that inhibitory phosphates on CDK-1, which is usually catalyzed by the Wee kinase family, were absent in
daf-21 (RNAi) animals. Furthermore, expression of WEE-1.3, one of the Wee kinase orthologs in C. elegans, was dramatically decreased in
daf-21 (RNAi) animals. These results suggest that
daf-21 function is required for proper expression, folding, or stability of WEE-1.3 in meiotic G2/M transition. All taken together, we propose that
daf-21 plays multiple roles by pleiotropically regulating distinct signaling pathways during germline development in C. elegans.(1) Inoue, T. et al. 2003. Develop. Growth and Differ., 2003: 369-376.