Melatonin Is Required for the Circadian Regulation of Sleep

Sleep is an evolutionarily conserved behavioral state whose regulation is poorly understood. A classical model posits that sleep is regulated by homeostatic and circadian mechanisms. Several factors have been implicated in mediating the homeostatic regulation of sleep, but molecules underlying the circadian mechanism are unknown. Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at night in aanat2 mutants maintained in light/dark conditions, and the circadian regulation of sleep is abolished in free-running conditions. We find that melatonin promotes sleep downstream of the circadian clock as it is not required to initiate or maintain circadian rhythms. Additionally, we provide evidence that melatonin may induce sleep in part by promoting adenosine signaling, thus potentially linking circadian and homeostatic control of sleep

The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones

During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease

Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9

Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy. Cell replacement therapy, using Hcrt-expressing neurons generated in vitro, is a potentially useful therapeutic approach, but factors sufficient to specify Hcrt neurons are unknown. Using zebrafish as a high-throughput system to screen for factors that can specify Hcrt neurons in vivo, we identified the LIM homeobox transcription factor Lhx9 as necessary and sufficient to specify Hcrt neurons. We found that Lhx9 can directly induce hcrt expression and we identified two potential Lhx9 binding sites in the zebrafish hcrt promoter. Akin to its function in zebrafish, we found that Lhx9 is sufficient to specify Hcrt-expressing neurons in the developing mouse hypothalamus. Our results elucidate an evolutionarily conserved role for Lhx9 in Hcrt neuron specification that improves our understanding of Hcrt neuron development

The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones

During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease

Black hole accretion and host galaxies of obscured quasars in XMM-COSMOS

We explore the connection between black hole growth at the center of obscured quasars selected from the XMM-COSMOS survey and the physical properties of their host galaxies. We study a bolometric regime ( 8 x 10^45 erg/s) where several theoretical models invoke major galaxy mergers as the main fueling channel for black hole accretion. We confirm that obscured quasars mainly reside in massive galaxies (Mstar>10^10 Msun) and that the fraction of galaxies hosting such powerful quasars monotonically increases with the stellar mass. We stress the limitation of the use of rest-frame color-magnitude diagrams as a diagnostic tool for studying galaxy evolution and inferring the influence that AGN activity can have on such a process. We instead use the correlation between star-formation rate and stellar mass found for star-forming galaxies to discuss the physical properties of the hosts. We find that at z ~1, ~62% of Type-2 QSOs hosts are actively forming stars and that their rates are comparable to those measured for normal star-forming galaxies. The fraction of star-forming hosts increases with redshift: ~71% at z ~2, and 100% at z ~3. We also find that the the evolution from z ~1 to z ~3 of the specific star-formation rate of the Type-2 QSO hosts is in excellent agreement with that measured for star-forming galaxies. From the morphological analysis, we conclude that most of the objects are bulge-dominated galaxies, and that only a few of them exhibit signs of recent mergers or disks. Finally, bulge-dominated galaxies tend to host Type-2 QSOs with low Eddington ratios (lambda<0.1), while disk-dominated or merging galaxies have at their centers BHs accreting at high Eddington ratios (lambda > 0.1).Comment: Accepted by A&A. 20 pages, 16 figures, 2 tables. A version with higher resolution figures and SED fits of Appendix A is available at http://www.eso.org/~vmainier/QSO2/qso2.pd