Developmental regulation of ephA4 expression in the chick auditory brainstem

Abstract

The avian auditory brainstem nuclei nucleus magnocellularis (NM) and nucleus laminaris (NL) display highly precise patterns of neuronal connectivity. NM projects tonotopically to the dorsal dendrites of ipsilateral NL neurons and to the ventral dendrites of contralateral NL neurons. The precision of this binaural segregation is evident at the earliest developmental stage at which connections can be observed. We have begun to examine the possibility that Eph receptor tyrosine kinase signaling is involved in establishing these spatially segregated connections. The expression of the EphA4 tyrosine kinase was examined at several developmental stages. EphA4 is expressed in rhombomere 5, which contains progenitors for both NM and NL. In this rhombomere, the labeling becomes striped during the time that precursor cells migrate to the auditory anlage. At the precise time when NM-NL projections are forming, EphA4 expression in NL is asymmetric, with markedly higher expression in the dorsal NL neuropil than in the ventral neuropil, suggesting a possible role in guiding growing axons to the appropriate region. At later embryonic ages EphA4 expression is symmetric around NL, and is absent in NM. As auditory function matures, EphA4 expression decreases so that by 4 days after hatch no EphA4 antibody labeling is evident in the auditory brainstem nuclei.

Axon guidance in the auditory system: Multiple functions of Eph receptors

“…Eph protein signaling has a demonstrated role in both aspects of this projection. During the formation of these connections, which are seen by embryonic day 10 (E10), EphA4 is more heavily expressed on dorsal dendrites of NL (Cramer et al, 2000). In this dorsal region, a concentration gradient is seen so that high frequency regions display more expression than do low frequency regions (Person et al, 2004).…”

Differential Roles for EphA and EphB Signaling in Segregation and Patterning of Central Vestibulocochlear Nerve Projections

“…The differential expression of EphA4 and EphB2 at the nerve entry point may thus reflect a mechanism that helps determine boundaries of fiber tracts; these tracts may facilitate axon navigation using additional guidance cues to direct axons to their hindbrain targets. Contrary to what is seen up to the nerve entry point, central vestibular projections strongly express EphA4 [46,47]. The reduction of vestibular hindbrain compartments following EphA4-Fc treatment is consistent with a role for EphA4 in designating a border for this pathway.…”

Astrocyte-Secreted Factors Modulate a Gradient of Primary Dendritic Arbors in Nucleus Laminaris of the Avian Auditory Brainstem

“…Dendrites are reported to interact in direct contact with glia during the formation of dendritic spines via Eph receptor tyrosine kinases [55], [56]. We have shown that some of the Eph proteins are localized to NL dendrites and show tonotopic expression gradients in NL neurons and surrounding astrocytes [36], [57]. Because these receptors bind to membrane-associated ligands [58], [59], [60], it is unlikely that the factors secreted from astrocytes act directly through these receptors, but it remains possible that contact-mediated signaling from astrocytes provides additional regulation of NL neurons through these proteins.…”

“…TrkB and TrkC are expressed in NL throughout the NL neuropil during development [69], and TrkB is localized to the ventral neuropil after about E10 [57], [69], but does not appear to be expressed in a tonotopic gradient. TrkC has been found to be developmentally regulated in the mammalian ventral cochlear nucleus [70] and its ligand, NT3 can be localized along astrocytic processes in the rat cochlear nucleus [71].…”