title: A regulatory module controlling pharyngeal development and function in Caenorhabditis elegans.
abstract: In Caenorhabditis elegans, the differentiation and morphogenesis of the foregut are controlled by several transcriptional regulators and cell signaling events, and by PHA-1, an essential cytoplasmic protein of unknown function. Previously we have shown that LIN-35 and UBC-18-ARI-1 contribute to the regulation of pha-1 and pharyngeal development through the Zn-finger protein SUP-35/ZTF-21. Here we characterize SUP-37/ZTF-12 as an additional component of the PHA-1 network regulating pharyngeal development. SUP-37 is encoded by four distinct splice isoforms, which contain up to seven C2H2 Zn-finger domains, and is localized to the nucleus, suggesting a role in transcription. Similar to sup-35, sup-37 loss-of-function mutations can suppress both LOF mutations in pha-1 as well as synthetic-lethal double mutants, including lin-35; ubc-18, which are defective in pharyngeal development. Genetic, molecular, and expression data further indicate that SUP-37 and SUP-35 may act at a common step to control pharyngeal morphogenesis, in part through the transcriptional regulation of pha-1. Moreover, we find that SUP-35 and SUP-37 effect pharyngeal development through a mechanism that can genetically bypass the requirement for pha-1 activity. Unlike SUP-35, SUP-37 expression is not regulated by either the LIN-35 or UBC-18-ARI-1 pathways. In addition, SUP-37 carries out two essential functions that are distinct from its role in regulating pharyngeal development with SUP-35. SUP-37 is required within a subset of pharyngeal muscle cells to facilitate coordinated rhythmic pumping and in the somatic gonad to promote ovulation. These latter observations suggest that SUP-37 may be required for the orchestrated contraction of muscle cells within several tissues.
authors.affiliation: Department of Molecular Biology, College of Agriculture and Natural Resources, University of Wyoming, Laramie, WY 82071, USA. davidfay@uwyo.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Fay
authors.forename: Stanley R G
authors.initials: SR
authors.lastname: Polley
authors.forename: Jujiao
authors.initials: J
authors.lastname: Kuang
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kuzmanov
authors.forename: James W
authors.initials: JW
authors.lastname: Hazel
authors.forename: Kumaran
authors.initials: K
authors.lastname: Mani
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Veo
authors.forename: John
authors.initials: J
authors.lastname: Yochem
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D032342:Muscle Cells / Q000378:metabolism; D009154:Mutation; D010614:Pharynx / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C489033:PHA-1 protein, C elegans; C576145:ZTF-21 protein, C elegans