, 2010) and SR9011 as well as SR9009 regulate circadian behavior and metabolism (Solt

et al., 2012). Synthetic molecules binding to proteins of the ROR family have been identified as well (Kumar et al., 2011 and Wang et al., 2010); however, their action on the circadian clock and on diseases related to metabolism or mood disorders has not been established and is currently under investigation. The circadian system is undoubtedly involved in a spectrum of disorders including metabolic and mood disorders. Circadian dysfunction can be either a contributing factor or a consequence of disease. Therefore, targeting the circadian clock for strengthening homeostatic mechanisms may be a promising therapeutic aim. This may be achieved either by pharmacological agents or by strengthening the clock via natural input such as light and feeding. Circadian pharmacology has just witnessed its dawn and holds a strong future given the promise of newly discovered agents Dabrafenib ic50 and find more their effective modes of action. I apologize for not being able to include all of the relevant studies due to space limitations. I thank Drs. Jean-Luc Dreyer, Jürgen Ripperger, and Gurudutt Pendyala for comments

on the manuscript. Funding provided by the Swiss National Science Foundation, the State of Fribourg, the Swiss International Cooperative Program, and the Velux Foundation is gratefully acknowledged. “
“Brains comprise diverse neuronal cell types that are interconnected through precise patterns of synaptic connections to form functional neural networks. How different neurons distinguish between one another during circuit assembly is poorly understood. Several large families of homologous cell recognition proteins arising through alternative splicing or gene duplication have been shown to play important roles in neural circuit formation and function (Shapiro et al., 2007, Südhof, 2008 and Zipursky and Sanes, 2010). Although different isoforms of several of these protein families, clustered protocadherins and neurexins in mammals and Dscam1 proteins in Drosophila, exhibit isoform-specific binding properties

in vitro ( Boucard et al., 2005, Schreiner and Weiner, 2010 and Wojtowicz et al., next 2007), whether this specificity is required in vivo remains unknown. Here we address whether the exquisite binding specificity of Dscam1 proteins is essential for their function in neural circuit assembly. The Drosophila Dscam1 gene encodes many protein isoforms of the Ig superfamily through alternative splicing ( Schmucker et al., 2000). This includes 19,008 potential ectodomains tethered to the membrane by two alternative transmembrane segments ( Schmucker et al., 2000). Each isoform is defined by a unique combination of three variable Ig domains, numbered from the N terminus as Ig2, Ig3, and Ig7 ( Figure 1A). Biochemical studies showed that isoforms bind in trans to an identical isoform but only weakly or not at all to different isoforms ( Wojtowicz et al.