scholarly journals The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev193862
Author(s):  
James Matthew Ragle ◽  
Abigail L. Aita ◽  
Kayleigh N. Morrison ◽  
Raquel Martinez-Mendez ◽  
Hannah N. Saeger ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Nuclear Hormone Receptor ◽  
Model Systems ◽  
Residual Body ◽  
Major Sperm Protein ◽  
Sperm Protein ◽  
C Elegans ◽  
Gene Regulatory ◽  
Established Role

ABSTRACTIn 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 regulating C. elegans molting, we discovered that NHR-23/NR1F1 is also constitutively expressed in developing primary 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 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.

scholarly journals The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis

2020 ◽  
Author(s):  
James Matthew Ragle ◽  
Abigail L. Aita ◽  
Kayleigh N. Morrison ◽  
Raquel Martinez-Mendez ◽  
Hannah N. Saeger ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Nuclear Hormone Receptor ◽  
Model Systems ◽  
Residual Body ◽  
Major Sperm Protein ◽  
C Elegans ◽  
Summary Statement ◽  
Gene Regulatory ◽  
Established Role

AbstractIn 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 StatementA well-characterized regulator of C. elegans molting also unexpectedly controls the spermatogenesis program; our work provides insights into the gene regulatory networks controlling spermatogenesis.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

scholarly journals LEVERAGING DRUG-DRUG INTERACTIONS FOR PHARMACOLOGICAL EXTENSION OF HEALTHY LIFESPAN

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S616-S616
Author(s):  
Jan Gruber
Keyword(s):  
Drug Interactions ◽  
Regulatory Network ◽  
Pharmacological Interventions ◽  
Distinct Entity ◽  
Promising Alternative ◽  
C Elegans ◽  
Ageing Processes ◽  
Age Dependent ◽  
Gene Regulatory ◽  
Traditional Approaches

Abstract Traditional approaches aimed at delaying or preventing age-dependent diseases view each disease as a distinct entity, resulting from separate pathophysiological chains of events. However, it is becoming increasing clear that even in adult animals there remains significant plasticity in terms of ageing trajectories and lifespan, suggesting that targeting ageing processes directly may be a promising alternative strategy. However, to date effects of even the most efficacious pharmacological interventions are smaller than those of ageing mutations, even when targeting the same ageing pathways. Interestingly, it has been shown that simultaneously targeting multiple ageing pathways can result in lifespan benefits that are synergistic (more than additive). We have recently shown that dramatic lifespan and healthspan extension can also be archived by leveraging interactions between drugs targeting distinct subsets of the gene-regulatory network controlling ageing of C. elegans. These interventions were highly efficacious, even when animals were treated only as adults.

scholarly journals A developmental gene regulatory network for invasive differentiation of theC. elegansanchor cell

2019 ◽  
Author(s):  
Taylor N. Medwig-Kinney ◽  
Jayson J. Smith ◽  
Nicholas J. Palmisano ◽  
Sujata Tank ◽  
Wan Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Network ◽  
Cell Fate ◽  
Regulatory Network ◽  
Cell Biology ◽  
Type I ◽  
Cell Specification ◽  
C Elegans ◽  
Gene Regulatory ◽  
Anchor Cell

ABSTRACTCellular invasion is a key part of development, immunity, and disease. Using thein vivomodel ofC. elegansanchor cell invasion, we characterize the gene regulatory network that promotes invasive differentiation. The anchor cell is initially specified in a stochastic cell fate decision mediated by Notch signaling. Previous research has identified four conserved transcription factors,fos-1a(Fos),egl-43(EVI1/MEL),hlh-2(E/Daughterless) andnhr-67(NR2E1/TLX), that mediate anchor cell specification and/or invasive differentiation. Connections between these transcription factors and the underlying cell biology that they regulate is poorly understood. Here, using genome editing and RNA interference, we examine transcription factor interactions prior to and after anchor cell specification. During invasion we identify thategl-43,hlh-2, andnhr-67function together in a type I coherent feed-forward loop with positive feedback. Conversely, prior to specification, these transcription factors function independent of one another to regulate LIN-12 (Notch) activity. Together, these results demonstrate that, although the same transcription factors can function in fate specification and differentiated cell behavior, a gene regulatory network can be rapidly re-wired to reinforce a post-mitotic, pro-invasive state.SUMMARY STATEMENTBasement membrane invasion by theC. elegansanchor cell is coordinated by a dynamic gene regulatory network encompassing cell cycle dependent and independent sub-circuits.

scholarly journals Insights Into the Early Gene Regulatory Network Controlling Neural Crest and Placode Fate Choices at the Neural Border

2020 ◽  
Vol 11 ◽  
Author(s):  
Subham Seal ◽  
Anne H. Monsoro-Burq
Keyword(s):  
Neural Crest ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Cell Types ◽  
Model Systems ◽  
Early Gene ◽  
Secretory Cells ◽  
Peripheral Neurons ◽  
Gene Regulatory

The neural crest (NC) cells and cranial placodes are two ectoderm-derived innovations in vertebrates that led to the acquisition of a complex head structure required for a predatory lifestyle. They both originate from the neural border (NB), a portion of the ectoderm located between the neural plate (NP), and the lateral non-neural ectoderm. The NC gives rise to a vast array of tissues and cell types such as peripheral neurons and glial cells, melanocytes, secretory cells, and cranial skeletal and connective cells. Together with cells derived from the cranial placodes, which contribute to sensory organs in the head, the NC also forms the cranial sensory ganglia. Multiple in vivo studies in different model systems have uncovered the signaling pathways and genetic factors that govern the positioning, development, and differentiation of these tissues. In this literature review, we give an overview of NC and placode development, focusing on the early gene regulatory network that controls the formation of the NB during early embryonic stages, and later dictates the choice between the NC and placode progenitor fates.

scholarly journals Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network

2017 ◽  
Vol 114 (23) ◽  
pp. 5800-5807 ◽  
Author(s):  
William J. R. Longabaugh ◽  
Weihua Zeng ◽  
Jingli A. Zhang ◽  
Hiroyuki Hosokawa ◽  
Camden S. Jansen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
Notch Signaling ◽  
Gene Regulatory Network ◽  
Cell Fate ◽  
Regulatory Network ◽  
T Cell Development ◽  
Cell Specification ◽  
Gene Regulatory

T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment and relate them to other regulomes. We show that both activation and repression target genes can be bound by Bcl11b in vivo, and that Bcl11b effects overlap with E2A-dependent effects. The newly clarified role of Bcl11b distinguishes discrete components of commitment, resolving how innate lymphoid, myeloid, and dendritic, and B-cell fate alternatives are excluded by different mechanisms.

scholarly journals Large P body-like RNPs form in C. elegans oocytes in response to arrested ovulation, heat shock, osmotic stress, and anoxia and are regulated by the major sperm protein pathway

2008 ◽  
Vol 319 (2) ◽  
pp. 464
Author(s):  
Jennifer A. Schisa ◽  
Molly C. Jud ◽  
Michael J. Czerwinski ◽  
Megan P. Wood ◽  
Rachel A. Young ◽  
...  
Keyword(s):  
Heat Shock ◽  
Osmotic Stress ◽  
Major Sperm Protein ◽  
Sperm Protein ◽  
C Elegans
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