Eph and ephrin signaling in the development of the central auditory system

Abstract

Acoustic communication relies crucially on accurate interpretation of information about the intensity, frequency, timing, and location of diverse sound stimuli in the environment. To meet this demand, neurons along different levels of the auditory system form precisely organized neural circuits. The assembly of these precise circuits requires tight regulation and coordination of multiple developmental processes. Several groups of axon guidance molecules have proven critical in controlling these processes. Among them, the family of Eph receptors and their ephrin ligands emerge as one group of key players. They mediate diverse functions at multiple levels of the auditory pathway, including axon guidance and targeting, topographic map formation, as well as cell migration and tissue pattern formation. Here, we review our current knowledge of how Eph and ephrin molecules regulate different processes in the development and maturation of central auditory circuits.

Getting connected: Pathfinding and synaptogenesis in neural development, evolution, and disease

“…For audition, this is the range of frequencies that comprise speech or sound and consequently a frequency map generated in the cochlea is relayed to central targets and maintained along the auditory pathway. These topographic maps are established and maintained by axon guidance cues, and as described by Krasewicz and Wu 4 for the auditory system, this is mediated by Eph‐Ephrin signaling.…”

Topographic axonal projection at single-cell precision supports local retinotopy in the mouse superior colliculus

“…Retinotopic map formation in SC occurs during the first postnatal week in mice, involving both genetic and activity-dependent factors (Cang and Feldheim, 2013;Arroyo and Feller, 2016). These factors also play a key role in the development of a fine-scale organization in other sensory systems, such as the tonotopic map in the cochlear nucleus (Krasewicz and Yu, 2023), and the chemotopic map in the olfactory bulb where olfactory sensory neurons expressing the same olfactory receptor type project exclusively to the same single glomerulus (Imai et al, 2010).…”

“…While overall sensory map formation is genetically predetermined by molecular cues (e.g., ephrin-Eph signaling; Frisén et al, 1998;Krasewicz and Yu, 2023;and axon-axon interactions;Plas et al, 2005;Cioni et al, 2018), a precise topography is established only after refinement that involves spontaneous activity, such as retinal waves during development (Chandrasekaran et al, 2005;Arroyo and Feller, 2016), and eventually experience-driven alignment (McLaughlin et al, 2003). In particular, here we suggest that this refinement process of the retinocollicular projection during development should be extremely precise, to the extent that retinotopy arises at a single-cell resolution in adult animals (Figures 3 and 4).…”

“…Retinotopic map formation in SC occurs during the first postnatal week in mice, involving both genetic and activity-dependent factors (Cang and Feldheim, 2013; Arroyo and Feller, 2016). These factors also play a key role in the development of a fine-scale organization in other sensory systems, such as the tonotopic map in the cochlear nucleus (Krasewicz and Yu, 2023), and the chemotopic map in the olfactory bulb where olfactory sensory neurons expressing the same olfactory receptor type project exclusively to the same single glomerulus (Imai et al, 2010). While overall sensory map formation is genetically predetermined by molecular cues (e.g., ephrin-Eph signaling; Frisén et al, 1998; Krasewicz and Yu, 2023; and axon-axon interactions; Plas et al, 2005; Cioni et al, 2018), a precise topography is established only after refinement that involves spontaneous activity, such as retinal waves during development (Chandrasekaran et al, 2005; Arroyo and Feller, 2016), and eventually experience-driven alignment (McLaughlin et al, 2003).…”

“…These factors also play a key role in the development of a fine-scale organization in other sensory systems, such as the tonotopic map in the cochlear nucleus (Krasewicz and Yu, 2023), and the chemotopic map in the olfactory bulb where olfactory sensory neurons expressing the same olfactory receptor type project exclusively to the same single glomerulus (Imai et al, 2010). While overall sensory map formation is genetically predetermined by molecular cues (e.g., ephrin-Eph signaling; Frisén et al, 1998; Krasewicz and Yu, 2023; and axon-axon interactions; Plas et al, 2005; Cioni et al, 2018), a precise topography is established only after refinement that involves spontaneous activity, such as retinal waves during development (Chandrasekaran et al, 2005; Arroyo and Feller, 2016), and eventually experience-driven alignment (McLaughlin et al, 2003). In particular, here we suggest that this refinement process of the retinocollicular projection during development should be extremely precise, to the extent that retinotopy arises at a single-cell resolution in adult animals (Figures 3 and 4).…”