PT  - JOURNAL ARTICLE
AU  - Londen C. Johnson
AU  - Joseph Aguilera
AU  - Max T. Levenson
AU  - Andreas Rechtsteiner
AU  - An A. Vo
AU  - J. Matt Ragle
AU  - Jordan D. Ward
TI  - Conditional depletion reveals temporal requirements for the oscillating transcription factor NHR-23/NR1F1 in <em>C. elegans</em> larval progression
AID  - 10.1101/2021.10.27.465992
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.27.465992
4099  - http://biorxiv.org/content/early/2021/10/27/2021.10.27.465992.short
4100  - http://biorxiv.org/content/early/2021/10/27/2021.10.27.465992.full
AB  - Nematode molting is a remarkable process where the animals must essentially build a new epidermis underneath the old skin and then rapidly shed the old skin. The study of molting provides a gateway into the developmental program of many core cellular and physiological processes, such as oscillatory gene expression, coordinated intracellular trafficking, steroid hormone signaling, developmental timing, and extracellular remodeling. The nuclear hormone receptor NHR-23/NR1F1 is an important regulator of molting. Imaging and western blot time-courses revealed oscillatory NHR-23::GFP expression in the epithelium that closely followed the reported mRNA expression. Timed depletion experiments using the auxin-inducible degron system revealed that NHR-23/NR1F1 depletion early in a given larval stage caused animals to arrest with only weak molting defects, whereas later depletion resulted in highly penetrant severe molting and morphological defects. This larval arrest was independent of insulin signaling. Despite the weakly penetrant molting defects following early NHR-23/NR1F1 depletion, the epidermal barrier was defective suggesting that NHR-23/NR1F1 is necessary for establishing or maintaining this barrier. NHR-23/NR1F1 coordinates the expression of factors involved in molting, lipid transport/metabolism, and remodeling of the apical extracellular matrix. We propose that NHR-23/NR1F1 is a regulator in a recently discovered large-scale gene oscillatory network coordinating rhythmic skin regeneration.Summary Statement This work provides insight into how a recently discovered large-scale gene expression oscillator promotes rhythmic skin regeneration in C. elegans.Competing Interest StatementThe authors have declared no competing interest.