Summary The brain of Drosophila melanogaster contains ca. 150 circadian neurons [1] functionally divided into Morning and Evening cells that control peaks in daily behavioral activity at dawn and dusk, respectively [2, 3]. The PIGMENT-DISPERSING FACTOR (PDF) positive small ventral Lateral Neurons (sLNvs) promote morning behavior, while the PDF negative sLNv and the dorsal Lateral Neurons (LNds) generate evening activity. Much less is known about the ca. 120 Dorsal Neurons (DN1, 2 and 3). Using a Clk-GAL4 driver that specifically targets a subset of DN1s, we generated mosaic per0 flies with clock function restored only in these neurons. We found that the Clk4.1M-GAL4 positive DN1s promote only morning activity under standard (high light intensity) light:dark cycles. Surprisingly however, these circadian neurons generate a robust evening peak of activity under a temperature cycle in constant darkness. Using different light intensities and ambient temperatures, we resolved this apparent paradox. The DN1 behavioral output is under both photic and thermal regulation. High light intensity suppresses DN1-generated evening activity. Low temperature inhibits morning behavior, but it promotes evening activity under high light intensity. Thus, the Clk4.1M-GAL4 positive DN1s, or the neurons they target, integrate light and temperature inputs to control locomotor rhythms. Our study therefore reveals a novel mechanism contributing to the plasticity of circadian behavior.

Summary Background Daily behaviors in animals are determined by the interplay between internal timing signals from circadian clocks and environmental stimuli such as light. How these signals are integrated to produce timely and adaptive behavior is unclear. The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity. Results Mutants of a novel ion channel, narrow abdomen (na), lack a robust increase in activity in response to light and show reduced anticipatory behavior and free-running rhythms, providing a genetic link between photic responses and circadian clock function. We used tissue-specific rescue of na to demonstrate a role for ∼16-20 circadian pacemaker neurons, a subset of the DN1p, in mediating the acute response to the onset of light as well as morning anticipatory behavior. Circadian pacemaker neurons expressing the neuropeptide PIGMENT DISPERSING FACTOR are especially important for morning anticipation and free-running rhythms and send projections to the DN1p. We also demonstrate that DN1p Pdfr expression is sufficient to rescue, at least partially, Pdfr morning anticipation defects as well as defects in free-running rhythms including those in DN1 molecular clocks. Additionally, these DN1 clocks in wild-type flies are more strongly reset to timing changes in PDF clocks than other pacemaker neurons, suggesting they are direct targets. Conclusion Taken together, we demonstrate that the DN1p lie at the nexus of PDF and photic signaling to produce appropriate daily behavior.

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is an autosomal recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance and fatty liver. Here, we create the first murine model of BSCL2 by targeted disruption of seipin, the causative gene for BSCL2. Compared with their wild-type littermates, the seipin(-/-) mice are viable and of normal weight but display significantly reduced adipose tissue mass, hepatic steatosis, glucose intolerance and hyperinsulinemia. The levels of leptin and adiponectin were both significantly decreased in seipin(-/-) mice, so were non-esterified fatty acids upon fasting. Surprisingly, however, hypertriglyceridemia which is common in human BSCL, was not observed in seipin(-/-) mice. Our findings suggest a possible tissue-autonomous role of seipin in liver lipid storage. The availability of the seipin(-/-) mice should help elucidate the molecular function of seipin and lead to a better understanding of the many metabolic consequences of human BSCL2.

SummaryThe endometrial layer comprises luminal and glandular epithelia that both develop from the same simple layer of fetal uterine epithelium. Mechanisms of uterine epithelial progenitor self-renewal and differentiation are unclear. This study aims to systematically analyze the molecular and cellular mechanisms of uterine epithelial development by single-cell analysis. An integrated set of single-cell transcriptomic data of uterine epithelial progenitors and their differentiated progenies is provided. Additionally the unique molecular signatures of these cells, characterized by sequential upregulation of specific epigenetic and metabolic activities, and activation of unique signaling pathways and transcription factors, were also investigated. Finally a unique subpopulation of early progenitor, as well as differentiated luminal and glandular lineages, were identified. A complex cellular hierarchy of uterine epithelial development was thus delineated. Our study therefore systematically decoded molecular markers and a cellular program of uterine epithelial development that sheds light on uterine developmental biology.

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