Developmental plasticity and the response to nutrient stress in Caenorhabditis elegans.

Developmental plasticity refers the ability of an organism to adapt to various environmental stressors, one of which is nutritional stress. Caenorhabditis elegans require various nutrients to successfully progress through all the larval stages to become a reproductive adult. If nutritional criteria are not satisfied, development can slow or completely arrest. In poor growth conditions, the animal can enter various diapause stages, depending on its developmental progress. In C. elegans, there are three well-characterized diapauses: the L1 arrest, the dauer diapause, and adult reproductive diapause, each associated with drastic changes in metabolism and germline development. At the centre of these changes is AMP-activated protein kinase (AMPK). AMPK is a metabolic regulator that maintains energy homeostasis, particularly during times of nutrient stress. Without AMPK, metabolism is disrupted during dauer, leading to the rapid consumption of lipid stores as well as misregulation of metabolic enzymes, leading to reduced survival. During the L1 arrest and dauer diapause, AMPK is responsible for ensuring germline quiescence by modifying the germline chromatin landscape to maintain germ cell integrity until conditions improve. Similar to classic hormonal signalling, small RNAs also play a critical role in regulating development and behaviour in a cell non-autonomous fashion. Thus, during the challenges associated with developmental plasticity, AMPK summons an army of signalling pathways to work collectively to preserve reproductive fitness during these periods of unprecedented uncertainty.

Nutrient Sensing and Response Drive Developmental Progression in Caenorhabditis elegans.

In response to nutrient limitation, many animals, including Caenorhabditis elegans, slow or arrest their development. This process requires mechanisms that sense essential nutrients and induce appropriate responses. When faced with nutrient limitation, C. elegans can induce both short and long-term survival strategies, including larval arrest, decreased developmental rate, and dauer formation. To select the most advantageous strategy, information from many different sensors must be integrated into signaling pathways, including target of rapamycin (TOR) and insulin, that regulate developmental progression. Here, how nutrient information is sensed and integrated into developmental decisions that determine developmental rate and progression in C. elegans is reviewed.

C. elegans MANF Homolog Is Necessary for the Protection of Dopaminergic Neurons and ER Unfolded Protein Response.

Neurotrophic factors (NTFs) are important for the development, function, and survival of neurons in the mammalian system. Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are two recently identified members of a novel family of NTFs in vertebrates that function to protect dopaminergic neurons. Although these genes are conserved across eukaryotes, their mechanism of neuroprotection is not fully understood. Sequence searches for MANF/CDNF homologs in invertebrates have identified a single ortholog that is most related to MANF. Here we report the in vivo characterization of the MANF gene, manf-1, in the nematode Caenorhabditis elegans. We found that manf-1 mutants have an accelerated, age-dependent decline in the survival of dopaminergic neurons. The animals also show increased endoplasmic reticulum (ER) stress, as revealed by reporter gene expression analysis of hsp-4, an ER chaperone BiP/GRP78 homolog, suggesting that a failure to regulate the ER unfolded protein response (ER-UPR) may be a contributing factor to dopaminergic neurodegeneration. Expression studies of manf-1 revealed that the gene is broadly expressed in a pattern that matches closely with hsp-4. Consistent with the requirements of manf-1 in the ER-UPR, we found that aggregates of α-Synuclein, a major constituent of Lewy bodies, were significantly increased in body wall muscles of manf-1 mutant animals. Overall, our work demonstrates the important role of manf-1 in dopaminergic neuronal survival and the maintenance of ER homeostasis in C. elegans.

Packing on the Pounds in Response to Bacterial Growth Conditions.

Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C. elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.