This pattern would follow the precedent set by neurexins for widely expressed presynaptic regulators interacting with structurally unrelated postsynaptic ligands at different types of synapses ( Williams et al., 2010). Understanding how the brain assembles specific types of synapses between

the correct partner cells will require consideration of multiple parallel trans-synaptic signaling complexes, and the latrophilin-FLRT Vorinostat nmr complex is poised to be an important unit in accomplishing this task. Given the genetic association of LPHN3 mutations ( Arcos-Burgos et al., 2010, Arcos-Burgos et al., 2010, Domené et al., 2011, Jain et al., 2011, Martinez et al., 2011 and Ribasés et al., 2011) and FLRT3 copy number variations ( Lionel et al., 2011) with ADHD, further characterization of the FLRT3-LPHN3 complex may lead to a better understanding of the pathology and etiology of this disorder. Please GS-7340 ic50 see the Supplemental Experimental Procedures. We thank Katie Tiglio, Joseph Antonios, Christine Wu, and Tim Young for assistance with virus injections, virus and recombinant protein production, and antibody testing. This work was supported by the Brain and Behavior Research

Foundation (formerly NARSAD) (J.d.W.), Autism Speaks grant 2617 (D.C.), NIH fellowship F32AG039127 (J.N.S.), and NIH grants NS067216 (A.G.), NS064124 (A.G.), P41 RR011823 (J.R.Y.), and R01 MH067880 (J.R.Y.). “
“A hallmark of the mammalian neocortex is the arrangement of

functionally distinct neurons in six horizontal layers, which possess distinct properties in different sensory or motor areas (Leone et al., 2008 and Molyneaux et al., 2007). The importance of this arrangement is revealed when it is disturbed, such as in patients with brain malformations, which are largely also composed of neuronal dysplasia in the cerebral cortex (Bielas et al., 2004, Guerrini and Parrini, 2010 and Ross and Walsh, 2001). One group of malformations, periventricular heterotopia (PH), results in cortical gray matter (GM) of varying size located at the ventricular margin. These defects can be associated with epilepsy and mental retardation (Guerrini and Parrini, 2010). While PH is clinically heterogeneous and also exhibits locus heterogeneity, most of the X-linked cases are due to mutations in a gene encoding the F-actin binding phosphoprotein Filamin A (Guerrini and Parrini, 2010 and Robertson, 2004). A second group of neuronal migration disorders consists of mutations in genes encoding microtubule (MT)-associated proteins, like Doublecortin (DCX) and Lissencephaly-1 (LIS1), resulting in partial or incomplete migration of neurons to their cortical locations during development (Bielas et al., 2004 and Ross and Walsh, 2001).