Biology subjects

Rosbash, M.

Publications and source records attributed to Rosbash, M..

3 recordsLinked to original sources

bioRxiv2018

Allatostatin C/AstC-R2 is a Novel Pathway to Modulate Circadian Activity Pattern in Drosophila

Six neuropeptides are expressed within the Drosophila brain circadian network. Our previous mRNA profiling suggested that AllatostatinC is a seventh neuropeptide and specifically expressed in dorsal clock neurons (DN1s). Our results here show that AstC is indeed expressed in DN1s, where it oscillates. AstC is also expressed in two less well-characterized circadian neuronal clusters, the DN3s and lateral posterior neurons (LPNs). Behavioral experiments indicate that clock neuron-derived AstC is required to mediate evening locomotor activity under short (winter-like) photoperiods. The AstC-Receptor 2 (AstC-R2) is expressed in LNds, the clock neurons that drive evening locomotor activity, and AstC-R2 is required in these neurons to modulate the same short photoperiod evening phenotype. Ex vivo calcium imaging indicates that AstC directly inhibits a single LNd neuron. The results suggest that a novel AstC/AstC-R2 signaling pathway, from dorsal circadian neurons to an LNd, regulates the behavioral response to changing photoperiod in Drosophila.

neuroscience↗

bioRxiv2018

A circadian output circuit controls sleep-wake arousal threshold in Drosophila

The Drosophila core circadian circuit contains distinct groups of interacting neurons that give rise to diurnal sleep-wake patterns. Previous work showed that a subset of Dorsal Neurons 1 (DN1s) are sleep-promoting through their inhibition of activity-promoting circadian pacemakers. Here we show that these anterior-projecting DNs (APDNs) also \"exit\" the circadian circuitry and communicate with the homeostatic sleep center in higher brain regions to regulate sleep and sleep-wake arousal threshold. These APDNs connect to a small discrete subset of tubercular-bulbar neurons, which are connected in turn to specific sleep-centric Ellipsoid Body (EB)-Ring neurons of the central complex. Remarkably, activation of the APDNs produces sleep-like oscillations in the EB and also raises the arousal threshold, which requires neurotransmission throughout the circuit. The data indicate that this APDN-TuBusup-EB circuit temporally regulates sleep-wake arousal threshold in addition to the previously defined role of the TuBu-EB circuit in vision, navigation and attention.

neuroscience↗

bioRxiv2017

HyperTRIBE identifies many in vivo targets of a RNA-binding protein

We previously developed TRIBE, a method for the identification of cell-specific RNA binding protein targets. TRIBE expresses an RBP of interest fused to the catalytic domain (cd) of the RNA editing enzyme ADAR and performs Adenosine-to-Inosine editing on RNA targets of the RBP. However, target identification is limited by the low editing efficiency of the ADARcd. Here we describe HyperTRIBE, which carries a previously characterized hyperactive mutation (E488Q) of the ADARcd. HyperTRIBE identifies dramatically more editing sites, many of which are also edited by TRIBE but at a much lower editing frequency. HyperTRIBE therefore more faithfully recapitulates the known binding specificity of its RBP than TRIBE. In addition, separating RNA binding from the enhanced editing activity of the HyperTRIBE ADAR catalytic domain sheds light on the mechanism of ADARcd editing as well as the enhanced activity of the HyperADARcd.

molecular biology↗