Faculty Opinions recommendation of A bHLH Code for Sexually Dimorphic Form and Function of the C. elegans Somatic Gonad.

Abstract Specialized cells of the somatic gonad primordium of nematodes play important roles in the final form and function of the mature gonad. C. elegans hermaphrodites are somatic females that have a two-armed, U-shaped gonad that connects to the vulva at the midbody. The outgrowth of each gonad arm from the somatic gonad primordium is led by two female Distal Tip Cells (fDTC), while the Anchor Cell (AC) remains stationary and central to coordinate uterine and vulval development. The bHLH protein HLH-2 and its dimerization partners LIN-32 and HLH-12 had previously been shown to be required for fDTC specification. Here, we show that ectopic expression of both HLH-12 and LIN-32 in cells with AC potential transiently transforms them into fDTC-like cells. Furthermore, hlh-12 was known to be required for the fDTCs to sustain gonad arm outgrowth. Here, we show that ectopic expression of HLH-12 in the normally stationary AC causes displacement from its normal position, and that displacement likely results from activation of the leader program of fDTCs because it requires genes necessary for gonad arm outgrowth. Thus, HLH-12 is both necessary and sufficient to promote gonadal regulatory cell migration. As differences in female gonadal morphology of different nematode species reflect differences in the fate or migratory properties of the fDTCs or of the AC, we hypothesized that evolutionary changes in the expression of hlh-12 may underlie evolution of such morphological diversity. However, we were unable to identify an hlh-12 ortholog outside of Caenorhabditis. Instead, by performing a comprehensive phylogenetic analysis of all Class II bHLH proteins in multiple nematode species, we found that HLH-12 evolved within the Caenorhabditis clade, possibly by duplicative transposition of hlh-10. Our analysis suggests that control of gene regulatory hierarchies for gonadogenesis can be remarkably plastic during evolution without adverse phenotypic consequence.

Download Full-text

Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30

10.1101/871079 ◽

2019 ◽

Author(s):

Yasmine J. Liu ◽

Rebecca L. McIntyre ◽

Georges E. Janssens ◽

Evan G. Williams ◽

Jiayi Lan ◽

...

Keyword(s):

Synergistic Effect ◽

Mitochondrial Network ◽

Mitochondrial Translation ◽

C Elegans ◽

Form And Function ◽

Unfolded Protein ◽

Lysosome Biogenesis ◽

And Function ◽

Protein Response ◽

Mitochondrial Unfolded Protein Response

AbstractMitochondrial form and function, such as translation, are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, which is accompanied by a fragmented mitochondrial network. However, the causality between mitochondrial translation and morphology in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial network homeostasis by either blocking fission or fusion synergizes with the reduced mitochondrial translation to substantially prolong lifespan and stimulate stress response such as the mitochondrial unfolded protein response, UPRMT. Conversely, immobilizing the mitochondrial network through a simultaneous abrogation of fission and fusion reverses the lifespan increase induced by mitochondrial translation inhibition. Furthermore, we find that the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan, despite stimulating UPRMT, does not require it. Instead, this lifespan-extending synergy is exclusively dependent on the lysosome biogenesis and autophagy transcription factor HLH-30/TFEB. Altogether, our study reveals the mechanistic connections between mitochondrial translation and dynamics in regulating longevity.SUMMARYMitochondrial form and function are intimately intertwined. Liu et al. find the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan. This synergy is dependent on the induction of lysosome biogenesis through the nuclear localization of HLH-30.

Download Full-text

Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30

The Journal of Cell Biology ◽

10.1083/jcb.201907067 ◽

2020 ◽

Vol 219 (6) ◽

Cited By ~ 4

Author(s):

Yasmine J. Liu ◽

Rebecca L. McIntyre ◽

Georges E. Janssens ◽

Evan G. Williams ◽

Jiayi Lan ◽

...

Keyword(s):

Mitochondrial Dynamics ◽

Mitochondrial Network ◽

Mitochondrial Translation ◽

C Elegans ◽

Form And Function ◽

Unfolded Protein ◽

Lysosome Biogenesis ◽

And Function ◽

Protein Response ◽

Mitochondrial Unfolded Protein Response

Mitochondrial form and function are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, and is accompanied by a fragmented mitochondrial network. However, whether this link between mitochondrial translation and morphology is causal in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial network homeostasis by blocking fission or fusion synergizes with reduced mitochondrial translation to prolong lifespan and stimulate stress response such as the mitochondrial unfolded protein response, UPRMT. Conversely, immobilizing the mitochondrial network through a simultaneous disruption of fission and fusion abrogates the lifespan increase induced by mitochondrial translation inhibition. Furthermore, we find that the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan, despite stimulating UPRMT, does not require it. Instead, this lifespan-extending synergy is exclusively dependent on the lysosome biogenesis and autophagy transcription factor HLH-30/TFEB. Altogether, our study reveals the mechanistic crosstalk between mitochondrial translation, mitochondrial dynamics, and lysosomal signaling in regulating longevity.

Download Full-text

A cellular and regulatory map of the cholinergic nervous system of C. elegans

eLife ◽

10.7554/elife.12432 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 136

Author(s):

Laura Pereira ◽

Paschalis Kratsios ◽

Esther Serrano-Saiz ◽

Hila Sheftel ◽

Avi E Mayo ◽

...

Keyword(s):

Nervous System ◽

Sexually Dimorphic ◽

Anion Channels ◽

Inhibitory Neurotransmitter ◽

C Elegans ◽

Transcriptional Regulatory ◽

System Maps ◽

Transcriptional Regulatory Mechanisms ◽

And Function ◽

Cholinergic Neurotransmitter

Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly.

Download Full-text

Chapter 17 C. elegans Members of the DEG/ENaC Channel Superfamily: Form and Function

Current Topics in Membranes - Amiloride-Sensitive Sodium Channels - Physiology and Functional Diversity ◽

10.1016/s0070-2161(08)60965-x ◽

1999 ◽

pp. 297-314

Author(s):

Heather A. Thieringer ◽

Sukhvinder Sahota ◽

Itzhak Mano ◽

Monica Driscoll

Keyword(s):

C Elegans ◽

Form And Function ◽

And Function

Download Full-text

Recovery from transgenerational RNA silencing is driven by gene-specific homeostasis

10.1101/148700 ◽

2017 ◽

Author(s):

Sindhuja Devanapally ◽

Pravrutha Raman ◽

Samual Allgood ◽

Farida Ettefa ◽

Maigane Diop ◽

...

Keyword(s):

Rna Silencing ◽

Epigenetic Inheritance ◽

Target Sequence ◽

C Elegans ◽

Form And Function ◽

Parental Exposure ◽

Homologous Genes ◽

In Trans ◽

Successive Generations ◽

And Function

AbstractChanges in gene expression that last for multiple generations without changes in gene sequence have been reported in many plants and animals1–3. Cases of such transgenerational epigenetic inheritance (TEI) could support the ancestral origins of some diseases and drive evolutionary novelty. Here, we report that stably expressed sequences in C. elegans have features that provide a barrier against TEI. By using double-stranded RNA (dsRNA) targeting the same sequence in different genes, we show that genes typically recover from silencing within the germline in a few generations. A rare recombinant two-gene operon containing this target sequence that recovered poorly from induced silencing enabled us to delineate mechanisms that can perpetuate silencing. Parental exposure to dsRNA targeting one gene within this operon reveals two distinct phases of the resulting TEI: only the matching gene is silenced in early generations, but both can become silenced in later generations. However, silencing of both genes can be initiated within one generation by mating, which perturbs intergenerational RNA-based mechanisms such that silencing dominates for more than 250 generations. This stable RNA silencing can also reduce the expression of homologous sequences in different genes in trans within the germline, but the homologous genes recover expression after a few generations. These results suggest that stably expressed sequences are subject to feedback control that opposes TEI initiated by multiple mechanisms within the germline. We speculate that similar homeostatic mechanisms that enable recovery from epigenetic changes underlie the observed preservation of form and function in successive generations of living systems.

Download Full-text

Scanning tunneling microscopy (STM) of DNA and RNA

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100152148 ◽

1989 ◽

Vol 47 ◽

pp. 34-35

Author(s):

Patricia G. Arscott ◽

Gil Lee ◽

Victor A. Bloomfield ◽

D. Fennell Evans

Keyword(s):

Molecular Structures ◽

Inorganic Materials ◽

Resolving Power ◽

Scanning Tunneling ◽

Tunneling Microscopy ◽

Form And Function ◽

Dna And Rna ◽

Calf Thymus ◽

And Function ◽

The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

Download Full-text