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NHR-23 activity is necessary for C. elegans developmental progression and apical extracellular matrix structure and function

2023; The Company of Biologists; Volume: 150; Issue: 10 Linguagem: Inglês

10.1242/dev.201085

1477-9129

Londen C. Johnson, An A. Vo, John Clancy, Krista M Myles, Murugesan Pooranachithra, Joseph Aguilera, Max T. Levenson, Chloe Wohlenberg, Andreas Rechtsteiner, James Matthew Ragle, Andrew Chisholm, Jordan D. Ward,

Spaceflight effects on biology

Nematode molting is a remarkable process where animals must repeatedly build a new apical extracellular matrix (aECM) beneath a previously built aECM that is subsequently shed. The nuclear hormone receptor NHR-23 (also known as NR1F1) is an important regulator of C. elegans molting. NHR-23 expression oscillates in the epidermal epithelium, and soma-specific NHR-23 depletion causes severe developmental delay and death. Tissue-specific RNAi suggests that nhr-23 acts primarily in seam and hypodermal cells. NHR-23 coordinates the expression of factors involved in molting, lipid transport/metabolism and remodeling of the aECM. NHR-23 depletion causes dampened expression of a nas-37 promoter reporter and a loss of reporter oscillation. The cuticle collagen ROL-6 and zona pellucida protein NOAH-1 display aberrant annular localization and severe disorganization over the seam cells after NHR-23 depletion, while the expression of the adult-specific cuticle collagen BLI-1 is diminished and frequently found in patches. Consistent with these localization defects, the cuticle barrier is severely compromised when NHR-23 is depleted. Together, this work provides insight into how NHR-23 acts in the seam and hypodermal cells to coordinate aECM regeneration during development.