The NHR-23-regulated putative protease inhibitor mlt-11 gene is necessary for C. elegans cuticle structure and function.

Autor:	Ragle JM; Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA 95064, USA., Turzo A; Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA 95064, USA., Jackson A; Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA 95064, USA., Vo AA; Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA 95064, USA., Pham VT; Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA 95064, USA., Ward JD; Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA 95064, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 17. Date of Electronic Publication: 2024 Oct 17.
DOI:	10.1101/2024.05.12.593762
Abstrakt:	C. elegans molting offers a powerful entry point to understanding developmentally programmed apical extracellular matrix remodeling. However, the gene regulatory network controlling this process remains poorly understood. Focusing on targets of NHR-23, a key transcription factor that drives molting, we confirmed the Kunitz family protease inhibitor gene mlt-11 as an NHR-23 target. Through reporter assays, we identified NHR-23-binding sites that are necessary and sufficient for epithelial expression. We generated a translational fusion and demonstrated that MLT-11 is localized to the cuticle and lined openings to the exterior (vulva, rectum, mouth). We created a set of strains expressing varied levels of MLT-11 by deleting endogenous cis -regulatory element sequences. Combined deletion of two cis -regulatory elements caused developmental delay, motility defects, and failure of the cuticle barrier. Inactivation of mlt-11 by RNAi produced even more pronounced defects. mlt-11 is necessary to pattern every layer of the adult cuticle, suggesting a broad patterning role prior to the formation of the mature cuticle. Together these studies provide an entry point into understanding how individual cis -regulatory elements function to coordinate expression of oscillating genes involved in molting and how MLT-11 ensures proper cuticle assembly. Competing Interests: Competing interests The authors declare no competing or financial interests.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu