RT Journal Article SR Electronic T1 The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.11.147298 DO 10.1101/2020.06.11.147298 A1 James Matthew Ragle A1 Abigail L. Aita A1 Kayleigh N. Morrison A1 Raquel Martinez-Mendez A1 Hannah N. Saeger A1 Guinevere A. Ashley A1 Londen C. Johnson A1 Katherine A. Schubert A1 Diane C. Shakes A1 Jordan D. Ward YR 2020 UL http://biorxiv.org/content/early/2020/06/12/2020.06.11.147298.abstract AB In sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulation of C. elegans molting, we discovered NHR-23/NR1F1 is also constitutively expressed in developing 1° spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles (MOs) but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.Summary Statement A well-characterized regulator of C. elegans molting also unexpectedly controls the spermatogenesis program; our work provides insights into the gene regulatory networks controlling spermatogenesis.