Identification of a molecular basis for the juvenile sleep state.

Across species, sleep in young animals is critical for normal brain maturation. The molecular determinants of early life sleep remain unknown. Through an RNAi-based screen, we identified a gene, , required for sleep maturation in , a transcription factor, coordinates an early developmental program that prepares the brain to later execute high levels of juvenile adult sleep.

Changes in Female Drosophila Sleep following Mating Are Mediated by SPSN-SAG Neurons.

Female Drosophila melanogaster, like many other organisms, exhibit different behavioral repertoires after mating with a male. These postmating responses (PMRs) include increased egg production and laying, increased rejection behavior (avoiding further male advances), decreased longevity, altered gustation and decreased sleep. Sex Peptide (SP), a protein transferred from the male during copulation, is largely responsible for many of these behavioral responses, and acts through a specific circuit to induce rejection behavior and alter dietary preference.

Context-specific comparison of sleep acquisition systems in Drosophila.

Sleep is conserved across phyla and can be measured through electrophysiological or behavioral characteristics. The fruit fly, Drosophila melanogaster, provides an excellent model for investigating the genetic and neural mechanisms that regulate sleep. Multiple systems exist for measuring fly activity, including video analysis and single-beam (SB) or multi-beam (MB) infrared (IR)-based monitoring.

The Drosophila Circadian Clock Gates Sleep through Time-of-Day Dependent Modulation of Sleep-Promoting Neurons.

Study Objectives: Sleep is under the control of homeostatic and circadian processes, which interact to determine sleep timing and duration, but the mechanisms through which the circadian system modulates sleep are largely unknown. We therefore used adult-specific, temporally controlled neuronal activation and inhibition to identify an interaction between the circadian clock and a novel population of sleep-promoting neurons in Drosophila.

Methods: Transgenic flies expressed either dTRPA1, a neuronal activator, or Shibire(ts1), an inhibitor of synaptic release, in small subsets of neurons.

Cooperative interaction between phosphorylation sites on PERIOD maintains circadian period in Drosophila.

Circadian rhythms in Drosophila rely on cyclic regulation of the period (per) and timeless (tim) clock genes. The molecular cycle requires rhythmic phosphorylation of PER and TIM proteins, which is mediated by several kinases and phosphatases such as Protein Phosphatase-2A (PP2A) and Protein Phosphatase-1 (PP1). Here, we used mass spectrometry to identify 35 "phospho-occupied" serine/threonine residues within PER, 24 of which are specifically regulated by PP1/PP2A.

Investigating tonic Wnt signaling throughout the adult CNS and in the hippocampal neurogenic niche of BatGal and ins-TopGal mice.

Wnt/β-catenin signaling has a well-established role in the development of the central nervous system (CNS), and recent evidence is extending this role to include the regulation of adult hippocampal function, including neurogenesis within the dentate gyrus. While the neuroanatomical expression pattern of many canonical Wnt signaling components have been investigated, the sites of signal integration and functional downstream β-catenin activation remain comparatively less characterized in the adult CNS. Using two independent transgenic β-catenin-activated LacZ reporter mouse lines (BatGal and ins-TopGal), we demonstrate that Wnt/β-catenin signaling is active in discrete regions of the adult mouse CNS.

A frazzled/DCC-dependent transcriptional switch regulates midline axon guidance.

Precise wiring of the nervous system depends on coordinating the action of conserved families of proteins that direct axons to their appropriate targets. Slit-roundabout repulsion and netrin-deleted in colorectal cancer (DCC) (frazzled) attraction must be tightly regulated to control midline axon guidance in vertebrates and invertebrates, but the mechanism mediating this regulation is poorly defined. Here, we show that the Fra receptor has two genetically separable functions in regulating midline guidance in Drosophila.

Cytoplasmic domain requirements for Frazzled-mediated attractive axon turning at the Drosophila midline.

The conserved DCC ligand-receptor pair Netrin and Frazzled (Fra) has a well-established role in axon guidance. However, the specific sequence motifs required for orchestrating downstream signaling events are not well understood. Evidence from vertebrates suggests that P3 is important for transducing Netrin-mediated turning and outgrowth, whereas in C.

Independent functions of Slit-Robo repulsion and Netrin-Frazzled attraction regulate axon crossing at the midline in Drosophila.

Slit and Netrin and their respective neuronal receptors play critical roles in patterning axonal connections in the developing nervous system by regulating the decision of whether or not to cross the midline. Studies of both invertebrate and vertebrate systems support the idea that Netrin, secreted by midline cells, signals through DCC (Deleted in Colorectal Carcinoma)/UNC40/Frazzled receptors to attract commissural axons toward and across the midline, whereas Slit signals through Robo family receptors to prevent commissural axons from recrossing the midline, as well as to prevent ipsilateral axons from ever crossing. Recent evidence from both Xenopus neuronal cell culture and Drosophila genetics have suggested that these signals may interact more directly in a hierarchical relationship, such that one response extinguishes the other.

beta-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS.

alpha- and beta-Spectrin are major components of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins. Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation. Here, we demonstrate that beta-Spectrin is required in neurons for proper midline axon guidance in the Drosophila embryonic CNS.

Axon guidance at the midline: from mutants to mechanisms.

How axons in the developing nervous system successfully navigate to their correct targets is a fundamental problem in neurobiology. Understanding the mechanisms that mediate axon guidance will give important insight into how the nervous system is correctly wired during development and may have implications for therapeutic approaches to developmental brain disorders and nerve regeneration. Achieving this understanding will require unraveling the molecular logic that ensures the proper expression and localization of axon guidance cues and receptors, and elucidating the signaling events that regulate the growth cone cytoskeleton in response to guidance receptor activation.