Osborne N et al. (2021) Biochem Pharmacol "CYP4V2 fatty acid omega hydroxylase, a druggable target for the treatment of metabolic associated fatty liver disease (MAFLD)."

Leahy C, Song BJ, Hardwick JP, Osborne N, Kwang Lee Y

[Biochem Pharmacol, 2021]

Fatty acids are essential in maintaining cellular homeostasis by providing lipids for energy production, cell membrane integrity, protein modification, and the structural demands of proliferating cells. Fatty acids and their derivatives are critical bioactive signaling molecules that influence many cellular processes, including metabolism, cell survival, proliferation, migration, angiogenesis, and cell barrier function. The CYP4 Omega hydroxylase gene family hydroxylate various short, medium, long, and very-long-chain saturated, unsaturated and polyunsaturated fatty acids. Selective members of the CYP4 family metabolize vitamins and biochemicals with long alkyl side chains and bioactive prostaglandins, leukotrienes, and arachidonic acids. It is uncertain of the physiological role of different members of the CYP4 omega hydroxylase gene family in the metabolic control of physiological and pathological processes in the liver. CYP4V2 is a unique member of the CYP4 family. CYP4V2 inactivation in retinal pigment epithelial cells leads to cholesterol accumulation and Bietti's Crystalline Dystrophy (BCD) pathogenesis. This commentary provides information on the role CYP4V2 has in metabolic syndrome and nonalcoholic fatty liver disease progression. This is accomplished by identifying its role in BCD, its control of cholesterol synthesis and lipid droplet formation in c. elegans, and the putative function in cardiovascular disease and gastrointestinal/hepatic pathologies.

Sokolowski MB (1998) Neuron "Genes for normal behavioral variation: recent clues from flies and worms."

Sokolowski MB

[Neuron, 1998]

The question of how genes contribute to normal individual differences in behavior has captured our imagination for more than a century. Several fundamental questions come to mind. How do genes and their proteins act in the nervous system and in response to the environment in order to cause individual differences in behavior? Do genetic differences between natural variants arise from alterations in the structural or regulatory region of a gene? Can we predict which genes for behavior, identified by mutant analysis in the laboratory, will have natural allelic variation? Three groundbreaking studies (Osborne et al., 1997; Sawyer et al., 1997; de Bono and Bargmann, 1998) published in the past year demonstrate that we now have the knowledge and technological capability to address these questions empirically. Each study has successfully identified a single major gene for a given behavior and, with the aid of transgenic animals, shown that its gene product is responsible for naturally occurring individual differences

Gruber J et al. (2009) FEBS Lett "Deceptively simple but simply deceptive--Caenorhabditis elegans lifespan studies: considerations for aging and antioxidant effects."

Gruber J, Halliwell B, Ng LF, Poovathingal SK

[FEBS Lett, 2009]

The nematode worm Caenorhabditis elegans (C. elegans) is increasingly popular as a model organism for aging studies as well as for testing antioxidants and other compounds for effects on longevity. However, results in the literature are sometimes confusing and contradictory. This review introduces C. elegans as a model organism, discusses aspects that make it attractive for aging and antioxidant research, and addresses some problems and potential artifacts.

Fitch DH (2005) Curr Biol "Evolution: an ecological context for C. elegans."

Fitch DH

[Curr Biol, 2005]

Despite low global diversity among natural populations of Caenorhabditis elegans, neighboring populations can be as genetically distinct as strains from different continents, probably owing to transient bottlenecks and ongoing dispersal as a dauer larva. Selfing predominates in the wild, but rare outcrossing may also play an important role.

Felix MA (2004) Curr Biol "Genomes: a helpful cousin for our favourite worm."

Felix MA

[Curr Biol, 2004]

The recently published genome of the nematdoe Caenorhabditis briggsae provides a drastic improvement in structural annotation of the C. elegans genome, as well as a promising source of evolutionary comparisons.

Dodd RB et al. (2001) Glycobiology "Lectin-like proteins in model organisms: implications for evolution of carbohydrate-binding activity."

Drickamer K, Dodd RB

[Glycobiology, 2001]

Classes of intracellular lectins that recognize core-type structures and mediate intracellular glycoprotein trafficking are present in vertebrates, model invertebrates such as Caenorhabditis elegans and Drosophila melanogaster, plants, and yeasts. Lectins that recognize more complex structures at the cell surface, such as C-type lectins and galectins, are also found in invertebrate organisms as well as vertebrates, but the functions of these proteins have evolved differently in different animal lineages.

Das P et al. (1999) Cytokine Growth Factor Rev "Genetic approaches to TGFbeta signaling pathways."

Padgett RW, Das P, Maduzia LL

[Cytokine Growth Factor Rev, 1999]

In this review, we provide a summary of the genetic analysis of TGFBeta signal transduction, as well as its role in various human diseases and mouse models. We also use discoveries in the TGFBeta pathway as an example to highlight some of the techniques used in the invertebrate world of C. elegans and Drosophila to further our understanding of this, and other, signaling systems. The roles of such techniques in elucidating diverse pathways, as well as pathways of human disease genes, will become more important as the information from the genome projects increases and as the development of genetics tools to analyze them becomes more powerful. Given the conservation of signaling mechanisms, there will be increasing synergy between studies in invertebrates and vertebrates in future years for solving different cellular pathways.

Bird DM (2005) Ann Appl Biol "Model systems in agriculture: lessons from worms."

Bird DM

[Ann Appl Biol, 2005]

Genomic tools are expanding the utility of organisms originally developed as models for biomedical research as a means to address complex agricultural problems. Conversely, agricultural pests are serving as models to help unravel questions of basic biology. Examples from C. elegans and root-knot nematode of this two-way exchange are discussed.

Hasse S et al. (2016) Methods "TransgeneOmics--A transgenic platform for protein localization based function exploration."

Hasse S, Hyman AA, Sarov M

[Methods, 2016]

The localization of a protein is intrinsically linked to its role in the structural and functional organization of the cell. Advances in transgenic technology have streamlined the use of protein localization as a function discovery tool. Here we review the use of large genomic DNA constructs such as bacterial artificial chromosomes as a transgenic platform for systematic tag-based protein function exploration.

Moghal N et al. (1999) Curr Opin Cell Biol "Multiple positive and negative regulators of signaling by the EGF-receptor."

Sternberg PW, Moghal N

[Curr Opin Cell Biol, 1999]

Signaling via the epidermal growth factor (EGF)-receptor family is subject to regulation and modulation by multiple ligands, effectors and negative regulators, as well as regulation by heterodimerization between family members and crosstalk between heterologous signaling pathways. Besides serving as a paradigm for receptor tyrosine kinases in general, this family is crucial for development and is often mutated or amplified in human tumors.