Heo W et al. (2022) BMB Rep "The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans."

Hwang H, Heo W, Kim K, Kim J, Yu Y, Oh SH, Lee JH

[BMB Rep, 2022]

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between transacting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cisregulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes.

Rutkowski R et al. (2010) Nat Cell Biol "Tagging the dead: a bridging factor for Caenorhabditis elegans phagocyte receptors."

Gartner A, Rutkowski R

[Nat Cell Biol, 2010]

Recognition of apoptotic cells by phagocytic cells in Caenorhabditis elegans has been something of a mystery. A secreted transthyretin-like protein, TTR-52, has been identified as a bridging molecule between apoptotic cells and CED-1 on the phagocytic cells that engulf them.

Swain A et al. (1998) Nature "Developmental genetics. Too much sex is bad for males."

Swain A, Lovell-Badge R

[Nature, 1998]

Many species rely on chromosome-based systems-such as one X versus two X chromosomes-to trigger the differences between males and females. To do this they must find ways to count the sex chromosomes and to activate the process of dosage compensation, which corrects the imbalance of sex-linked genes. A paper by Carmi, Kopczynski and Meyer on page 168 of this issue brings us closer to understand chromosome counting in the nematode worm Caenorhabditis elegans. The authors have identified an X-linked gene that encodes a protein related to nuclear-hormone receptors. This protein, SEX-1, represses the transcription of xol-1, the pivotal gene involved in both dosage compensation and sex determination.

Tavernarakis N et al. (2001) Curr Biol "Structural and functional features of the intracellular amino terminus of DEG/ENaC ion channels."

Driscoll M, Tavernarakis N, Everett JK, Kyrpides NC

[Curr Biol, 2001]

The degenerin/epithelial sodium channel (DEG/ ENaC) protein family includes related ion channel subunits from organisms ranging from the simple nematode Caenorhabditis elegans to humans. Members of this protein family have been implicated in functions as diverse as touch transduction and proprioception [1-4], pain sensation and maintenance of sodium balance [5].

Thomas JH (1999) Nature "Lifespan. The effects of sensory deprivation."

Thomas JH

[Nature, 1999]

Once, lifespan genetics was largely the domain of theorists, who tried to explain why an organism's genes so cavalierly allow individual somas to die. But a flood of papers on the nematode worm Caenorhabditis elegans has brought the subject into the realm of serious experimental analysis. The latest studies (1,2), including a report by Apfeld and Kenyon (1) on page 804 of this issue, indicate that the nervous system has a key function in regulating lifespan. Perhaps we are, indeed, only as old as we think

Drescher U (1996) Nature "Netrins find their receptor."

Drescher U

[Nature, 1996]

What guides migrating nerve axons to their correct targets during development? This is one of the basic issues in developmental neurobiology, and chemoattraction has long been thought to be involved. A tangible answer began to emerge with the demonstration that explants of rat spinal floorplate promoted the outgrowth of axons from commissural neurons, and caused these axons to turn. Subsequently, the specific factors concerned in axon turning were identified. These factors, called netrin-1 and netrin-2, are phlogenetically conserved molecules related to the product of the unc-6 gene in Caenorhabditis elegans.

Mlot C (1991) Science "A well-rounded worm."

Mlot C

[Science, 1991]

The millimeter-long roundworm Caenorhabditis elegans is amassing a sizable research following. As more and more people have joined teh confederation of research efforts loosely called the worm project (see Science, 15 June 1990, p. 1310), the community's biennial meeting has outgrown the traditional watering hole at Cold Spring Harbor. This year, the researchers moved inland for the Eighth International C. elegans Meeting, held June 1-5 on Lake Mendota at the University of Wisconsin, Madison. More than 500 "worm people" turned out to absorb progress reports on the sequencing of the C. elegans genome, the study of its developmental pathways-and some newer topics as well.

Durnaoglu S et al. (2020) BMB Rep "Human Endogenous Retrovirus K (HERV-K) can drive gene expression as a promoter in Caenorhabditis elegans."

Ahnn J, Durnaoglu S, Lee SK, Kim HS

[BMB Rep, 2020]

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans (C. elegans) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b, a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues.

Altintas O et al. (2015) BMB Rep "The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C. elegans and D. melanogaster."

Altintas O, Park S, Lee SV

[BMB Rep, 2015]

Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) pathway regulates aging in many organisms ranging from simple invertebrates to mammals including humans. Many seminal discoveries regarding the roles of IIS in aging and longevity have been made by using the roundworm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. In this review, we describe mechanisms by which various IIS components regulate aging in C. elegans and D. melanogaster. We also cover systemic and tissue-specific effects of the IIS components on the regulation of lifespan. We further discuss IIS-mediated physiological processes other than aging and its effects on human disease models focusing on findings that used C. elegans. As both C. elegans and D. melanogaster have been essential for key findings regarding the effects of IIS on organismal aging in general, these invertebrate models will continue to serve as workhorses to help our understanding of mammalian aging.

Emmons SW et al. (1999) Nature "Signal transduction. Mating, channels and kidney cysts."

Somlo S, Emmons SW

[Nature, 1999]

Advances in human genetics have meant that the genes mutated in human diseases can be identified exclusively by their location in the genome. But how do we work out the cellular functions of the associated protein products? Reports on pages 383 and 386 of this issue begin to address this problem for two proteins - polycystin-1 (PKD1) and polycystin-2 (PKD2) - that are defective in human kidney disease. From their studies of the nematode worm Caenorhabditis elegans, Barr and Sternberg present evidence that homologues of the polycystins act together in a signal-transduction pathway in sensory neurons. Chen et al., by contrast, have used an oocyte-expression system in the from Xenopus laevis to show that a homologue of PKD2 is associated with the activity of a cation channel. These results support the hypothesis that polycystin-related proteins belong to a hitherto unknown class of signal-transduction molecules.