Semaphorins and hair cell wiring

Type I SGNs synapse with inner hair cells, whereas type II SGNs extend their peripheral axons past pillar cells to synapse with outer hair cells. The mechanisms regulating the differential projection of  SGNs to their appropriate targets is critical to the normal function of the auditory system but have remained largely unknown.  Class-3 secreted Semaphorins (Sema3s) bind to Neuropilin/Plexin (Nrp/Plxn) co-receptors to regulate diverse aspects of neuron motility and development in many regions of the nervous system. Our data indicate that several Sema3s are expressed within distinct domains of the cochlear epithelium at developmental times that correlate with the arrival of SGN peripheral axons, which express Neuropilin receptors. In this project, we are using a combination of mouse genetics and in vitro techniques, as well as time lapse imaging to determine the function(s) of secreted Semaphorins in cochlear innervation. Photo above left: an early postnatal cochlea immunostained with anti-myosin 6 antibodies (blue; hair cells) and genetic labeling of sparse numbers of SGNs (from the Neurog1CreERT2 line from the Goodrich laboratory).  

Intercellular communication between SGNs and the cochlear mesenchyme

 Radial axon bundles are critical for appropriate wiring patterns in the cochlea, but the molecular mechanisms controlling their formation are not well understood. This project stems directly from our work on Pou3f4 in the control of SGN axon fasciculation in which we identified ephrin-B2 as a binding partner for the Pou3f4 target gene, Epha4/EphA4 (Coate et al., 2012, Neuron). In addition to Epha4, we found several additional axon guidance candidates that appear to be regulated by Pou3f4. In this project, we will examine these factors in cochlear innervation and investigate their functional importance. Left: a whole-mount preparation of a cochlea immunostained with anti-Tuj1 (green; SGNs and efferents), anti-Sox10 (blue; glia) and anti-Pou3f4 (red; mesenchyme) antibodies.