Feedforward regulatory logic controls the specification-to-differentiation transition and terminal cell fate during Caenorhabditis elegans endoderm development.

Autor:	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.; Chemical and Biomolecular Engineering Department, University of California Los Angeles, Los Angeles, CA 90095, USA., Flowers SE; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA., Maduro MF; Molecular, Cell and Systems Biology Department, University of California Riverside, Riverside, CA 92521, USA., Joshi PM; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA., Rothman JH; Department of MCD Biology and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.; Program in Biomolecular Science and Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2022 Jun 15; Vol. 149 (12). Date of Electronic Publication: 2022 Jun 27.
DOI:	10.1242/dev.200337
Abstrakt:	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. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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