Eph-ephrin signaling in nervous system development.

Ephrins and Eph receptors enable contact-mediated interactions between cells at every stage of nervous system development. In spite of their broad binding affinities, Eph proteins facilitate specificity in neuronal migration and axon targeting. This review focuses on recent studies that demonstrate how these proteins interact with each other, and with other signaling pathways, to guide specificity in a diverse set of developmental processes.

Ephrin-B reverse signaling is required for formation of strictly contralateral auditory brainstem pathways.

Specificity in the projections from the mammalian ventral cochlear nucleus (VCN) is essential for sound localization. Globular bushy cells project from the VCN to the medial nucleus of the trapezoid body (MNTB) on the contralateral, but not the ipsilateral, side of the brainstem, terminating in large synaptic endings known as calyces of Held. The precision in this pathway is critical for the computation of interaural intensity differences, which are used in sound localization.

Transient gain adjustment in the inferior colliculus is serotonin- and calcium-dependent.

In the inferior colliculus (IC), a brief period of acoustic conditioning can transiently enhance evoked discharge rate. The cellular basis of this phenomenon was assessed with whole cell current-clamp recordings in a gerbil IC brain slice preparation. The current needed to elicit a single action potential was first established for each neuron.

Auditory brainstem responses are impaired in EphA4 and ephrin-B2 deficient mice.

The Eph receptor tyrosine kinases and their membrane-anchored ligands, ephrins, are signaling proteins that act as axon guidance molecules during chick auditory brainstem development. We recently showed that Eph proteins also affect patterns of neural activation in the mammalian brainstem. However, functional deficits in the brainstems of mutant mice have not been assessed physiologically.

Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice.

Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates.