title: MED GATA factors promote robust development of the C. elegans endoderm.
abstract: The MED-1,2 GATA factors contribute to specification of E, the progenitor of the Caenorhabditis elegans endoderm, through the genes end-1 and end-3, and in parallel with the maternal factors SKN-1, POP-1 and PAL-1. END-1,3 activate elt-2 and elt-7 to initiate a program of intestinal development, which is maintained by positive autoregulation. Here, we advance the understanding of MED-1,2 in E specification. We find that expression of end-1 and end-3 is greatly reduced in med-1,2(-) embryos. We generated strains in which MED sites have been mutated in end-1 and end-3. Without MED input, gut specification relies primarily on POP-1 and PAL-1. 25% of embryos fail to make intestine, while those that do display abnormal numbers of gut cells due to a delayed and stochastic acquisition of intestine fate. Surviving adults exhibit phenotypes consistent with a primary defect in the intestine. Our results establish that MED-1,2 provide robustness to endoderm specification through end-1 and end-3, and reveal that gut differentiation may be more directly linked to specification than previously appreciated. The results argue against an "all-or-none" description of cell specification, and suggest that activation of tissue-specific master regulators, even when expression of these is maintained by positive autoregulation, does not guarantee proper function of differentiated cells.
authors.affiliation: Biology Department, University of California, Riverside, Riverside, CA 92521, United States. Electronic address: mmaduro@ucr.edu.
authors.forename: Morris F
authors.initials: MF
authors.lastname: Maduro
authors.affiliation: Biology Department, University of California, Riverside, Riverside, CA 92521, United States.
authors.forename: Gina
authors.initials: G
authors.lastname: Broitman-Maduro
authors.affiliation: Cell, Molecular and Developmental Biology Graduate Program, University of California, Riverside, Riverside, CA, United States.
authors.forename: Hailey
authors.initials: H
authors.lastname: Choi
authors.affiliation: MARCU-STAR Program, University of California, Riverside, Riverside, CA, United States.
authors.forename: Francisco
authors.initials: F
authors.lastname: Carranza
authors.affiliation: Graduate Program in Bioinformatics and Systems Biology, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Allison Chia-Yi
authors.initials: AC
authors.lastname: Wu
authors.affiliation: Section of Ecology, Behavior, and Evolution, Division of Biology, University of California, San Diego, La Jolla, CA, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rifkin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D050980:GATA Transcription Factors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C109211:END-1 protein, C elegans; C504457:END-3 protein, C elegans; D050980:GATA Transcription Factors; C433251:MED-1 protein, C elegans; C433252:MED-2 protein, C elegans; D014157:Transcription Factors
keywords: C. elegans; Cell specification; Endoderm; GATA factors; Gene regulation; Gene regulatory networks; Robustness