title: Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.
abstract: In multicellular organisms, genetic programs guide cells to adopt cell fates as tissues are formed during development, maintained in adults, and repaired after injury. Here we explore how a small molecule in the environment can switch a genetic program from one fate to another. Wild-type Caenorhabditis elegans XX adult hermaphrodites make oocytes continuously, but certain mutant XX adults make sperm instead in an otherwise hermaphrodite soma. Thus, puf-8; lip-1 XX adults make only sperm, but they can be switched from sperm to oocyte production by treatment with a small-molecule MEK inhibitor. To ask whether this chemical reprogramming is common, we tested six XX sperm-only mutants, but found only one other capable of cell fate switching, fbf-1; lip-1. Therefore, reprogramming competence relies on genotype, with only certain mutants capable of responding to the MEK inhibitor with a cell fate change. To gain insight into the molecular basis of competence for chemical reprogramming, we compared polyadenylated transcriptomes of competent and noncompetent XX sperm-only mutants in the absence of the MEK inhibitor and hence in the absence of cell fate reprogramming. Despite their cellular production of sperm, competent mutants were enriched for oogenic messenger RNAs relative to mutants lacking competence for chemical reprogramming. In addition, competent mutants expressed the oocyte-specific protein RME-2, whereas those lacking competence did not. Therefore, mutants competent for reprogramming possess an intersexual molecular profile at both RNA and protein levels. We suggest that this intersexual molecular signature is diagnostic of an intermediate network state that poises the germline tissue for changing its cellular fate in response to environmental cues.
authors.affiliation: Graduate Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Elena P
authors.initials: EP
authors.lastname: Sorokin
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Audrey P
authors.initials: AP
authors.lastname: Gasch
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706 Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 Howard Hughes Medical Institute, University of Wisconsin, Madison, Wisconsin 53706 jekimble@wisc.edu.
authors.forename: Judith
authors.initials: J
authors.lastname: Kimble
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D008297:Male; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D009928:Organ Specificity; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019849:Sex Determination Processes; D013094:Spermatozoa / Q000378:metabolism; D059467:Transcriptome
chemical_list: D002070:Butadienes; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D009570:Nitriles; C510538:PUF-8 protein, C elegans; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C113580:U 0126; D020930:MAP Kinase Kinase Kinases; C421904:lip-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases
keywords: MAPK signaling; PUF protein; germline; network states; sex determination