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Feedforward regulatory logic controls the specification-to-differentiation transition and terminal cell fate during Caenorhabditis elegans endoderm development.
Ewe, Chee Kiang; Sommermann, Erica M; Kenchel, Josh; Flowers, Sagen E; Maduro, Morris F; Joshi, Pradeep M; Rothman, Joel H.
Afiliação
  • Ewe CK; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
  • Sommermann EM; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
  • Kenchel J; Program in Biomolecular Science and Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
  • Flowers SE; Chemical and Biomolecular Engineering Department, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Maduro MF; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
  • Joshi PM; Molecular, Cell and Systems Biology Department, University of California Riverside, Riverside, CA 92521, USA.
  • Rothman JH; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
Development ; 149(12)2022 06 15.
Article em En | MEDLINE | ID: mdl-35758255
The architecture of gene regulatory networks determines the specificity and fidelity of developmental outcomes. We report that the core regulatory circuitry for endoderm development in Caenorhabditis elegans operates through a transcriptional cascade consisting of six sequentially expressed GATA-type factors that act in a recursive series of interlocked feedforward modules. This structure results in sequential redundancy, in which removal of a single factor or multiple alternate factors in the cascade leads to a mild or no effect on gut development, whereas elimination of any two sequential factors invariably causes a strong phenotype. The phenotypic strength is successfully predicted with a computational model based on the timing and levels of transcriptional states. We found that one factor in the middle of the cascade, END-1, which straddles the distinct events of specification and differentiation, functions in both processes. Finally, we reveal roles for key GATA factors in establishing spatial regulatory state domains by repressing other fates, thereby defining boundaries in the digestive tract. Our findings provide a paradigm that could account for the genetic redundancy observed in many developmental regulatory systems.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caenorhabditis elegans / Proteínas de Caenorhabditis elegans Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Caenorhabditis elegans / Proteínas de Caenorhabditis elegans Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article