title: Cell shape and Wnt signaling redundantly control the division axis of C. elegans epithelial stem cells.
abstract: Tissue-specific stem cells combine proliferative and asymmetric divisions to balance self-renewal with differentiation. Tight regulation of the orientation and plane of cell division is crucial in this process. Here, we study the reproducible pattern of anterior-posterior-oriented stem cell-like divisions in the Caenorhabditis elegans seam epithelium. In a genetic screen, we identified an alg-1 Argonaute mutant with additional and abnormally oriented seam cell divisions. ALG-1 is the main subunit of the microRNA-induced silencing complex (miRISC) and was previously shown to regulate the timing of postembryonic development. Time-lapse fluorescence microscopy of developing larvae revealed that reduced alg-1 function successively interferes with Wnt signaling, cell adhesion, cell shape and the orientation and timing of seam cell division. We found that Wnt inactivation, through mig-14 Wntless mutation, disrupts tissue polarity but not anterior-posterior division. However, combined Wnt inhibition and cell shape alteration resulted in disordered orientation of seam cell division, similar to the alg-1 mutant. Our findings reveal additional alg-1-regulated processes, uncover a previously unknown function of Wnt ligands in seam tissue polarity, and show that Wnt signaling and geometric cues redundantly control the seam cell division axis.
authors.affiliation: Department of Developmental Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. wildwaterm@gmail.com
authors.forename: Marjolein
authors.initials: M
authors.lastname: Wildwater
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sander
authors.forename: Geert
authors.initials: G
authors.lastname: de Vreede
authors.forename: Sander
authors.initials: S
authors.lastname: van den Heuvel
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D016764:Cell Polarity; D048430:Cell Shape; D018509:DNA, Helminth / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D009154:Mutation; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C558782:ALG-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D016601:RNA-Binding Proteins; D051153:Wnt Proteins; D051176:beta Catenin