lin-4 (miR-125) microRNAs are deeply conserved across animal phylogeny. They are among the first microRNAs discovered and were implicated in regulating developmental timing in C. elegans. In this study, we report that mutations in lin-4 microRNA specifically suppress the AVM axon guidance defects in slt-1 mutants through enhancement of netrin attraction. lin-4 expression in AVM neurons rescued lin-4 mutant phenotypes in AVM axon guidance, suggesting that lin-4 acts cell autonomously in AVM to inhibit its axon attraction to netrin. lin-4 is expressed strongly in the AVM neuron when its axon guidance is underway, and is almost undetectable in the ALM neuron whose axon guidance is netrin independent. The transcription factor lin-14, a necessary target of lin-4 microRNA in the AVM neurons, stimulates netrin-mediated AVM axon ventral guidance. lin-14’s positive effect in netrin attraction is mediated by the receptor unc-40 (DCC) and its cofactor madd-2 functioning through a combination of the unc-34 (Ena) and ced-10 (Rac1)-dependent downstream pathways. lin-14 stimulates netrin-mediated axon attraction in part by enhancing UNC-40 protein expression. Our study indicates that the eventual down-regulation of lin-14 activity in the AVM neurons at the end of axon guidance is caused by lin-4 microRNA inhibition.
The gut plays a central role in energy homeostasis. Food intake regulation strongly relies on the gut–brain axis, and numerous studies have pointed out the significant role played by gut hormones released from enteroendocrine cells. It is well known that digestive products of dietary protein possess a high satiating effect compared to carbohydrates and fat. Nevertheless, the processes occurring in the gut during protein digestion involved in the short-term regulation of food intake are still not totally unraveled. This review provides a concise overview of the current data concerning the implication of food-derived peptides in the peripheral regulation of food intake with a focus on the gut hormones cholecystokinin and glucagon-like peptide 1 regulation and the relationship with some aspects of glucose homeostasis.
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