SUMMARY Studies in mammals have indicated a connection between circadian clocks and feeding behavior, but the nature of the interaction, and its relationship to nutrient metabolism, are not understood. In Drosophila clock proteins are expressed in many metabolically important tissues, but have not been linked to metabolic processes. Here we demonstrate that Drosophila feeding behavior displays a 24-hour circadian rhythm which is regulated by clocks in digestive/metabolic tissues. Flies lacking clocks in these tissues, in particular in the fat body, also display increased food consumption, but have decreased levels of glycogen and a higher sensitivity to starvation. Interestingly, glycogen levels and starvation sensitivity are also affected by clocks in neuronal cells but the effects of neuronal clocks generally oppose those of the fat body. We propose that the input of neuronal clocks and clocks in metabolic tissues is coordinated to provide effective energy homeostasis.

Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae. We found that Fmr1 could be detected in the cell bodies and proximal dendrites of DA neurons and that Fmr1loss-of-function mutations increased the number of higher-order dendritic branches. Conversely, overexpression of Fmr1 in DA neurons dramatically decreased dendritic branching. In dissecting the mechanisms underlying Fmr1 function in dendrite development, we found that the mRNA encoding small GTPase Rac1 was present in the Fmr1-messenger ribonucleoprotein complexes in vivo. Mosaic analysis with a repressor cell marker (MARCM) and overexpression studies revealed that Rac1 has a cell-autonomous function in promoting dendritic branching of DA neurons. Furthermore, Fmr1 and Rac1 genetically interact with each other in controlling the formation of fine dendritic branches. These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect.

Circadian rhythms are regulated by a synchronized system of central and peripheral clocks. Here we show that a clock in the Drosophila fat body drives rhythmic expression of genes involved in metabolism, detoxification, the immune response and steroid hormone regulation. Some of these genes cycle even when the fat body clock is disrupted indicating they are regulated by exogenous factors. Food is an important stimulus as limiting food availability to a six-hour interval each day drives rhythmic expression of genes in the fat body. Restricting food to a time of day when consumption is typically low desynchronizes internal rhythms because it alters the phase of rhythmic gene expression in the fat body without affecting the brain clock. Flies maintained on this paradigm produce fewer eggs than those restricted to food at the normal time. These data suggest that desynchrony of endogenous rhythms, caused by aberrant feeding patterns, affects reproductive fitness.