Ch8 Nematodes metabolism

• Hormonal control of nematode metabolism and diapause is mediated by biogenic amines, neuropeptides, insulin-like peptides, TGF-β-like peptides, steroids, and pheromones.
• Nematode dauer hormones play a role in behavioral states and metabolism and aging.
• The life cycle of Caenorhabditis elegans consists of four larval stages, separated by moults.
• A C. elegans hermaphrodite has 959 somatic cells (302 neurons) and a complete cell lineage.
• Caenorhabditis elegans has a complete genome sequence (~19,000 genes) and powerful genetic techniques available.
• Caenorhabditis elegans has many robust behavioral assays and a cellular-level anatomical structure, including a largely complete neuronal wiring diagram.
• Caenorhabditis elegans is an important experimental organism with each cell identified by position, synapses identified for each neuron, and neuronal structure determined by EM.
• TGB-β signaling controls dauer in nematodes.
• DAF-4 (Type II receptor) is shared with the dauer pathway, but other components are distinct.
• Nematode dauer hormones mimic the responses of wild-type worms under unfavorable conditions, implying that DAF-7 is normally released in favorable conditions, stress inhibits release/production.
• TGF-β signaling also controls body size.
• DAF-3 is a co-SMAD in the dauer pathway.
• DAF-5 and Sno/Ski are txn factors in the dauer pathway.
• Mammalian adrenal 28 Group 2 dauer mutants are known as Daf-c Daf-d.
• DAF-4, DAF-14 are Ser/Thr kinases in the dauer pathway.
• R-SMADs and co-SMADs are involved in the dauer pathway.
• Dauer pheromone inhibits the expression of DAF-7/TGF-β in the ASI neuron.
• DAF-7 and TGF-β ligand are two key components in the dauer pathway.
• Insulin and IGF act through RTKs, while relaxins act through GPCRs.
• DAF-28 inhibits dauer development.
• Daf-2 dauers (caused by IR activation) do not have low DAF-28.
• Dachronic acid is involved in reproductive development.
• The C. elegans genome is comparable to 8 in the fly and 10 in the human.
• DAF-28::GFP is expressed in ASI and ASJ.
• Nematode dauer hormonal signaling involves ASI, ASJ, other neurons, epidermis, and dauer development.
• TGF-β, INS, and cGMP are involved in dauer hormonal signaling.
• A dominant negative allele of daf-28 has a Daf-c phenotype.
• DAF-28 levels in ASI and ASJ are reduced in dauers.
• Nematode dauer hormones include DAF-28, insulin, TGF-β, and pheromone.
• Daf-28 is expressed in a few neurons, including ASI and ASJ.
• The synthesis of dafachronic acids from cholesterol involves DAF-36 (Reiske oxygenase) and DAF-9 (cytochrome P450), which are enzymes required for dafachronic acid synthesis.
• The genetic discovery of the dauer steroid pathway involves daf-12 null mutants being Daf-d, other alleles being Daf-c, and epistasis experiments placing daf-12 downstream of all other mutant alleles.
• Humans have 48 nuclear receptor genes, and Drosophila has 18.
• daf-9 generates a steroid ligand for DAF-12 NHR.
• Other than DAF-12, the ligands for the worm nuclear receptors are unknown.
• Unbound DAF-12 promotes transcription of dauer genes.
• daf-12 encodes a nuclear receptor, and daf-9 encodes an enzyme in steroid metabolism.
• In mammals, an analogous pathway generates bile acids, which are ligands for the farnesoid X nuclear receptor.
• C. elegans has a huge family of nuclear hormone receptors, with 284 different nuclear receptor genes in the genome.
• Dafachronic acids are released by the skin in a favorable environment, promoting normal postembryonic development and inhibiting dauer development.