Howard Hughes Medical Institute; Department of Molecular Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA.
Howard Hughes Medical Institute; Department of Molecular Cellular and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA.
Dev Cell. 2015 May 4;33(3):260-71. doi: 10.1016/j.devcel.2015.02.015. Epub 2015 Apr 16.
Food deprivation suppresses animal growth and development but spares the systems essential for foraging. The mechanisms underlying this selective development, and potential roles of lipids in it, are unclear. When C. elegans hatch in a food-free environment, postembryonic growth and development stall, but sensory neuron differentiation and neuronal development required for food responses continue. Here, we show that monomethyl branched-chain fatty acids (mmBCFAs) and their derivative, d17iso-glucosylceramide, function in the intestine to promote foraging behavior and sensory neuron maturation through both TORC1-dependent and -independent mechanisms. We show that mmBCFAs impact the expression of a subset of genes, including ceh-36/Hox, which we show to play a key role in mediating the regulation of the neuronal functions by this lipid pathway. This study uncovers that a lipid pathway promotes neuronal functions involved in foraging under both fed and fasting conditions and adds critical insight into the physiological functions of TORC1.
食物剥夺会抑制动物的生长和发育,但会保留觅食所必需的系统。这种选择性发育的机制以及脂质在其中的潜在作用尚不清楚。当秀丽隐杆线虫在无食物的环境中孵化时,其胚胎后生长和发育停滞,但对食物反应所必需的感觉神经元分化和神经元发育仍在继续。在这里,我们表明单甲基支链脂肪酸(mmBCFAs)及其衍生物 d17iso-葡糖基神经酰胺在肠道中通过 TORC1 依赖和非依赖机制发挥作用,以促进觅食行为和感觉神经元成熟。我们表明,mmBCFAs 影响一组基因的表达,包括 ceh-36/Hox,我们表明该基因在介导脂质途径对神经元功能的调节中起着关键作用。这项研究揭示了一条脂质途径在进食和禁食条件下均能促进与觅食相关的神经元功能,并为 TORC1 的生理功能提供了重要的见解。