Rothman J et al. (2019) Genetics "Developmental Plasticity and Cellular Reprogramming in Caenorhabditiselegans."

Jarriault S, Rothman J

[Genetics, 2019]

While <i>Caenorhabditis elegans</i> was originally regarded as a model for investigating determinate developmental programs, landmark studies have subsequently shown that the largely invariant pattern of development in the animal does not reflect irreversibility in rigidly fixed cell fates. Rather, cells at all stages of development, in both the soma and germline, have been shown to be capable of changing their fates through mutation or forced expression of fate-determining factors, as well as during the normal course of development. In this chapter, we review the basis for natural and induced cellular plasticity in <i>C. elegans</i> We describe the events that progressively restrict cellular differentiation during embryogenesis, starting with the multipotency-to-commitment transition (MCT) and subsequently through postembryonic development of the animal, and consider the range of molecular processes, including transcriptional and translational control systems, that contribute to cellular plasticity. These findings in the worm are discussed in the context of both classical and recent studies of cellular plasticity in vertebrate systems.

McGhee JD (1987) Biochemistry "Purification and characterization of a carboxylesterase from the intestine of the nematode Caenorhabditis elegans."

McGhee JD

[Biochemistry, 1987]

The major intestinal esterase from the nematode Caenorhabditis elegans has been purified to essential homogeneity. Starting from whole worms, the overall purification is 9000-fold with a 10% recovery of activity. The esterase is a single polypeptide chain of Mr 60,000 and is stoichiometrically inhibited by organophosphates. Substrate preferences and inhibition patterns classify the enzyme as a carboxylesterase (EC 3.1.1.1), but the physiological function is unknown. The sequence of 13 amino acid residues at the esterase N- terminus has been determined. This partial sequence shows a surprisingly high degree of similarity to the N-terminal sequence of two carboxylesterases recently isolated from Drosophila mojavensis [Pen, J., van Beeumen, J., & Beintema, J. J. (1986) Biochem. J. 238, 691-699].

Spickard, E. et al. (2017) International Worm Meeting "Transcriptome and functional analysis of ELT-7-directed reprogramming and transorganogenesis of the C. elegans gonad and pharynx."

Rothman, J., Spickard, E.

[International Worm Meeting, 2017]

Organogenesis is a tightly controlled process that ensures a robust and stable developmental output through regulatory mechanisms that buffer against changes in the fates of cells once they have differentiated. We have found that post-mitotic, fully differentiated cells of the C. elegans pharynx, and cells undergoing organogenesis of the somatic gonad, can be redirected to develop into an intestine-like organ by forced expression of the ELT-7 GATA-type transcription factor. This reprogramming, which does not require inhibition of other factors or the generation of dedifferentiated intermediates, occurs within 20 hours of ELT-7 induction. The reprogrammed somatic gonad, which has undergone what we have called "transorganogenesis," is virtually indistinguishable at the ultrastructural level from that of the endogenous intestine. To investigate the mechanisms of this cell fate switching, we analyzed the transcriptional profiles of worms during early transorganogenesis by mRNA-seq. Statistical comparison of worm transcriptomes at three hours after hs-elt-7 induction, versus a hs-gfp control, identified over 5,000 strongly differentially expressed transcripts. Tissue enrichment analysis of differentially expressed genes (DEGs) revealed specificity for somatic gonad-related genes based on anatomy ontology terms, particularly among genes that are downregulated by ELT-7. These results suggest that, while the hs-elt-7 construct is expressed globally, the somatic gonad is specifically susceptible to alterations in gene expression patterns. Transcription factor binding site (TFBS) predictions for DEGs that are upregulated by ELT-7 reveal enrichment for GATA binding sites, indicating that a significant fraction of early transcriptional changes may be attributable to the direct activity of ELT-7 and/or other GATA factors. TFBS analysis also shows enrichment for forkhead box and homeobox binding sites. To test the functional relevance of these associations, our mRNA-seq results are being used to guide a candidate RNAi screen for factors that are critical for transdifferentiation and transorganogenesis.

Murakami S et al. (1999) Curr Biol "Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene."

Johnson TE, Murakami S

[Curr Biol, 1999]

In this Brief Communication, which appeared in the 14 September 1998 issue of Current Biology, the UV dose was reported erroneously. The dose reported was 20 J/m2 but the actual dose used was 0.4 J/cm2. Also, the gene formally referred to as tkr-1 has since been renamed old-1 (overexpression longevity determination).

Ramos CG et al. (2014) J Bacteriol "Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia."

Feliciano JR, da Costa PJ, Ramos CG, Grilo AM, Leitao JH

[J Bacteriol, 2014]

Volume 195, no. 16, p. 35143523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitao, J. Bacteriol. 193:15151526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Nillegoda NB et al. (2015) Nature "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation."

Berynskyy M, Morimoto RI, Bukau B, Stengel F, Kirstein J, Szlachcic A, Arnsburg K, Stank A, Scior A, Nillegoda NB, Gao X, Guilbride DL, Aebersold R, Wade RC, Mayer MP

[Nature, 2015]

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control.

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Sommer RJ et al. (1994) Worm Breeder's Gazette "Evolution of Vulva-Formation: Part II: Species With a Central Vulva"

Sommer RJ, Sternberg PW

[Worm Breeder's Gazette, 1994]

Evolution of vulva-formation: Part II: Species with a central vulva Ralf J. Sommer & Paul W. Sternberg, California Institute of Technology, Division of Biology 156-29, Pasadena, CA 91125

Jun-ichi Aikawa (2001) International C. elegans Meeting "Molecular characterization of heparan sulfate/heparin N-deacetylase/N-sulfotransferase in worms"

Jun-ichi Aikawa

[International C. elegans Meeting, 2001]

Heparan sulfate binds and activates a large variety of growth factors, enzymes and extracellular matrix proteins. These interactions largely depend on the specific arrangement of sulfated moieties and uronic acid epimers within the chains. These oligosaccharide sequences are generated in a step-wise manner, initiated by the formation of a linkage tetrasaccharide which is then extended by copolymerization of alternating a1,4GlcNAc and b1,4GlcA residues. As the chains polymerize, they undergo a series of sulfation and epimerization reactions. The first set of modifications involves the removal of acetyl units from subsets of GlcNAc residues, and the addition of sulfate groups to the resulting free amino groups. These reactions are catalyzed by a family of enzymes designated as GlcNAc N-deacetylase/N-sulfotransferases (NDST), since they simultaneously. Four members of the family have been identified in vertebrates, with single orthologs present in Drosophila and C. elegans. We have revealed tissue-specific expression pattern and unique enzymatic properties of these four isozymes1,2). In fly, loss of NDST (sulfateless) results in unsulfated chains and defective signaling by multiple growth factors and morphogens. I reconstituted cDNA for worm NDST from EST clones and 5' RACE products. Enzymatic activities will be discussed. 1) Aikawa, J. & Esko, J. D J. Biol. Chem. 274, 2690-2695 (1999) 2) Aikawa, J., Grobe, K., Tsujimoto, M. & Esko, J. D J. Biol. Chem. 276, 5876-5882 (2001)

Suman, Shashi Kumar et al. (2021) International Worm Meeting "Characterization of two evolutionarily conserved C. elegans Ceh-6/Oct and Sox-2/Sox2 transcriptional factors during a natural Y-to PDA transdifferentiation event"

Daulny, Anne, Suman, Shashi Kumar, Ahier, Arnaud, Jarriault, Sophie, Le Gal, Thomas

[International Worm Meeting, 2021]

During trans-differentiation, a differentiated cell changes its identity and becomes another different specialized cell. This process is also known as direct cell conversion or direct reprogramming and plays an important role in development, tissue regeneration and diseases. In C. elegans, our lab has pioneered the study of natural trans-differentiation, several examples of which are now documented, starting from embryonic to larval development and including Y-to-PDA transdifferentiation (Jarriault et al., 2008, Rothman &amp; Jarriault &amp;, 2019). Initially, the Y cell, together with the other five cells forms the functional rectum of C. elegans and harbor specialized epithelial features. During larval development, it naturally transdifferentiates, acquires neuronal cell identity, and becomes a PDA motoneuron. This process is governed by various molecular players such as chromatin remodelers and transcription factors (Kagias et al 2012, Zuryn et al 2015). Previous work from the lab has shown that the C. elegans POU transcription factor CEH-6 and SOX-2 form, with other genes, a NODE-like complex (NODE mammalian counterpart) and are important for the initiation of this reprogramming event. Here, through genetics and biochemical studies, we have analyzed the characteristics of C. elegans sox-2 and ceh-6 and have compared them to their mammalian counterparts. We have dissected their function over time and which domains are important for Y-to-PDA Td. We have further tested putative functional redundancy with the other two Pou paralogs ceh-18 and unc-86, and mammalian Oct4. Our work highlights both conserved and divergent molecular mechanisms underlying different reprogramming processes. Rothman J &amp; Jarriault S.(2019) Genetics 213(3):723-757. Zuryn S, et al. (2014) Science 345(6198):826-829. Jarriault S, et al. (2008) Proc Natl Acad Sci U S A 105(10):3790-3795. Kagias K, et al. (2012) Proc Natl Acad Sci U S A 109(17):6596-6601. Liang J, et al. (2008) Nature cell biology 10(6):731-739.