Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System of Drosophila

Axonal insulation is critical for efficient action potential propagation and normal functioning of the nervous system. I

A Laminin G-EGF-Laminin G Module in Neurexin IV Is Essential for the Apico-Lateral Localization of Contactin and Organization of Septate Junctions

Septate junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons

ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection

Selective processing of behaviorally relevant sensory inputs against irrelevant ones is a fundamental cognitive function whose impairment has been implicated in major psychiatric disorders. It is known that the thalamic reticular nucleus (TRN) gates sensory information en route to the cortex, but the underlying mechanisms remain unclear. Here we show in mice that deficiency of the Erbb4 gene in somatostatin-expressing TRN neurons markedly alters behaviors that are dependent on sensory selection. Whereas the performance of the Erbb4-deficient mice in identifying targets from distractors was improved, their ability to switch attention between conflicting sensory cues was impaired. These behavioral changes were mediated by an enhanced cortical drive onto the TRN that promotes the TRN-mediated cortical feedback inhibition of thalamic neurons. Our results uncover a previously unknown role of ErbB4 in regulating cortico-TRN-thalamic circuit function. We propose that ErbB4 sets the sensitivity of the TRN to cortical inputs at levels that can support sensory selection while allowing behavioral flexibility