Scharf A et al. (2021) Front Cell Dev Biol "Reproductive Aging in Caenorhabditis elegans: From Molecules to Ecology."

Pohl F, Egan BM, Kornfeld K, Scharf A, Kocsisova Z

[Front Cell Dev Biol, 2021]

Aging animals display a broad range of progressive degenerative changes, and one of the most fascinating is the decline of female reproductive function. In the model organism Caenorhabditis elegans, hermaphrodites reach a peak of progeny production on day 2 of adulthood and then display a rapid decline; progeny production typically ends by day 8 of adulthood. Since animals typically survive until day 15 of adulthood, there is a substantial post reproductive lifespan. Here we review the molecular and cellular changes that occur during reproductive aging, including reductions in stem cell number and activity, slowing meiotic progression, diminished Notch signaling, and deterioration of germ line and oocyte morphology. Several interventions have been identified that delay reproductive aging, including mutations, drugs and environmental factors such as temperature. The detailed description of reproductive aging coupled with interventions that delay this process have made C. elegans a leading model system to understand the mechanisms that drive reproductive aging. While reproductive aging has dramatic consequences for individual fertility, it also has consequences for the ecology of the population. Population dynamics are driven by birth and death, and reproductive aging is one important factor that influences birth rate. A variety of theories have been advanced to explain why reproductive aging occurs and how it has been sculpted during evolution. Here we summarize these theories and discuss the utility of C. elegans for testing mechanistic and evolutionary models of reproductive aging.

Lecroisey C et al. (2007) J Muscle Res Cell Motil "The C. elegans dense body: anchoring and signaling structure of the muscle."

Gieseler K, Lecroisey C, Segalat L

[J Muscle Res Cell Motil, 2007]

During evolution, both the architecture and the cellular physiology of muscles have been remarkably maintained. Striated muscles of invertebrates, although less complex, strongly resemble vertebrate skeletal muscles. In particular, the basic contractile unit called the sarcomere is almost identical between vertebrates and invertebrates. In vertebrate muscles, sarcomeric actin filaments are anchored to attachment points called Z-disks, which are linked to the extra-cellular matrix (ECM) by a muscle specific focal adhesion site called the costamere. In this review, we focus on the dense body of the animal model Caenorhabditis elegans. The C. elegans dense body is a structure that performs two in one roles at the same time, that of the Z-disk and of the costamere. The dense body is anchored in the muscle membrane and provides rigidity to the muscle by mechanically linking actin filaments to the ECM. In the last few years, it has become increasingly evident that, in addition to its structural role, the dense body also performs a signaling function in muscle cells. In this paper, we review recent advances in the understanding of the C. elegans dense body composition and function.

Qadota H et al. (2010) J Biomed Biotechnol "Molecular structure of sarcomere-to-membrane attachment at M-Lines in C. elegans muscle."

Qadota H, Benian GM

[J Biomed Biotechnol, 2010]

C. elegans is an excellent model for studying nonmuscle cell focal adhesions and the analogous muscle cell attachment structures. In the major striated muscle of this nematode, all of the M-lines and the Z-disk analogs (dense bodies) are attached to the muscle cell membrane and underlying extracellular matrix. Accumulating at these sites are many proteins associated with integrin. We have found that nematode M-lines contain a set of protein complexes that link integrin-associated proteins to myosin thick filaments. We have also obtained evidence for intriguing additional functions for these muscle cell attachment proteins.

Ziegler C (1994) Comp Biochem Physiol A Physiol "Titin-related proteins in invertebrate muscles."

Ziegler C

[Comp Biochem Physiol A Physiol, 1994]

The localization of filaments connecting the Z-line and the A-band in insect flight muscles and the identification of very large proteins as their components is reviewed. The characterization of twitchin in the obliquely striated muscles of Caenorhabditis elegans is reported and the deductions made from its amino acid sequence are considered. The characterization of mini-titins in obliquely striated molluscan muscles is compared. The identification of projectin in the muscles of Drosophila melanogaster by anti-twitchin-antibodies, its sequence analysis and the characterization of mini-titins in arthropod and mollusc fast-striated muscles are summarized. The possible biological functions of the different proteins in various invertebrate muscles are discussed.

Bullard B et al. (2002) J Muscle Res Cell Motil "Varieties of elastic protein in invertebrate muscles."

Leonard K, Linke WA, Bullard B

[J Muscle Res Cell Motil, 2002]

Elastic proteins in the muscles of a nematode (Caenorhabditis elegans), three insects (Drosophila melanogaster, Anopheles gambiae, Bombyx mori) and a crustacean (Procambus clarkii) were compared. The sequences of thick filament proteins, twitchin in the worm and projectin in the insects, have repeating modules with fibronectin-like (Fn) and immunoglobulin-like (Ig) domains conserved between species. Projectin has additional tandem Igs and an elastic PEVK domain near the N-terminus. All the species have a second elastic protein we have called SLS protein after the Drosophila gene, sallimus. SLS protein is in the I-band. The N-terminal region has the sequence of kettin which is a spliced product of the gene composed of Ig-linker modules binding to actin. Downstream of kettin, SLS protein has two PEVK domains, unique sequence, tandem Igs, and Fn domains at the end. PEVK domains have repeating sequences: some are long and highly conserved and would have varying elasticity appropriate to different muscles. Insect indirect flight muscle (IFM) has short I-bands and electron micrographs of Lethocerus IFM show fine filaments branching from the end of thick filaments to join thin filaments before they enter the Z-disc. Projectin and kettin are in this region and the contribution of these to the high passive stiffness of Drosophila IFM myofibrils was measured from the force response to length oscillations. Kettin is attached both to actin near the Z-disc and to the end of thick filaments, and extraction of actin or digestion of kettin leads to rapid decrease in stiffness; residual tension is attributable to projectin. The wormlike chain model for polymer elasticity fitted the force-extension curve of IFM myofibrils and the number of predicted Igs in the chain is consistent with the tandem Igs in Drosophila SLS protein. We conclude that passive tension is due to kettin and projectin, either separate or

Lucchesi JC (2018) J Genet "Transcriptional modulation of entire chromosomes: dosage compensation."

Lucchesi JC

[J Genet, 2018]

Dosage compensation is a regulatory system designed to equalize the transcription output of the genes of the sex chromosomes that are present in different doses in the sexes (X or Z chromosome, depending on the animal species involved). Different mechanisms of dosage compensation have evolved in different animal groups. In Drosophila males, a complex (male-specific lethal) associates with the X chromosome and enhances the activity of most X-linked genes by increasing the rate of RNAPII elongation. In Caenorhabditis, a complex (dosage compensation complex) that contains a number of proteins involved in condensing chromosomes decreases the level of transcription of both X chromosomes in the XX hermaphrodite. In mammals, dosage compensation is achieved by the inactivation, early during development, of most X-linked genes on one of the two X chromosomes in females. The mechanism involves the synthesis of an RNA (Tsix) that protects one of the two Xs from inactivation, and of another RNA (Xist) that coats the other X chromosome and recruits histone and DNA modifying enzymes. This review will focus on the current progress in understanding the dosage compensation mechanisms in the three taxa where it has been best studied at the molecular level: flies, round worms and mammals.

Burr AHJ et al. (1998) Biol Bull "Mechanical significance of obliquely striated architecture in nematode muscle."

Burr AHJ, Gans C

[Biol Bull, 1998]

In certain invertebrate muscles, adjacent narrow columns of sarcomeres are displaced along the fiber axis, providing an obliquely striated myofilament pattern in certain section planes. Although this architecture is described in many phyla and has been the subject of much discussion (1-12), its mechanical significance has yet to be resolved. In nematodes, where ultrastructural details of the obliquely striated muscle have long been known (12-19), another unique and prominent feature is the attachment of every sarcomere to the plasmalemma and basal lamina via dense bodies (Z-disc analogs). Unfortunately, the importance of this feature to the transmission of the contractile force to the cuticle is not understood outside the Caenorhabditis elegans literature: it was overlooked in recent reviews covering obliquely striated muscle (9-11). Here we consider transmission of force and oblique striation together. We compare the contractile architecture in C. elegans with that in the more complex muscle type of larger nematodes. Both types are designed to transmit the force of contraction laterally to the cuticle rather than longitudinally to the muscle ends. In the second type, folding of the contractile structure around an inward extension of the basal lamina enables a higher number of sarcomeres to be linked to cuticle per unit length. We suggest that the mechanical significance of the oblique arrangement of sarcomeres in both types is that it distributes the force application sites of the sarcomeres more evenly over the basal lamina and cuticle. With this muscle architecture, smooth bending of the nematode body tube would be possible, and kinking would be prevented.