Expression of EphB receptors and EphrinB ligands in the developing chick auditory brainstem

Cramer, Karina S.; Karam, Sana D.; Bothwell, Mark; Cerretti, Douglas Pat; Pasquale, Elena B.; Rubel, Edwin W.

doi:10.1002/cne.10399

Cited by 37 publications

(39 citation statements)

References 149 publications

(179 reference statements)

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“…Netrin-DCC signaling is required to establish proper axonal projections from the VCN in mouse embryos (Howell et al, 2007). Eph/Ephrin signaling is also known to play an important role in establishing auditory brainstem circuits in chick embryos (Cramer et al, 2002(Cramer et al, , 2006. In contrast to embryonic auditory development, molecules involved in the postnatal development of auditory pathways remain elusive.…”

Section: Nb-2 Expression Is Transient In the Soc And Just Precedes Thmentioning

confidence: 96%

Preferential localization of neural cell recognition molecule NB‐2 in developing glutamatergic neurons in the rat auditory brainstem

Toyoshima

Sakurai

Shimazaki

et al. 2009

J of Comparative Neurology

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NB-2 is a neuronal cell recognition molecule that is preferentially expressed in auditory pathways. Mice deficient in the NB-2 gene exhibit aberrant responses to acoustic stimuli. Here we examined the expression and localization of NB-2 in the auditory brainstem during development in the rat. NB-2 was strongly expressed in the ventral cochlear nucleus (VCN), ventral acoustic stria, lateral and medial superior olivary complex (SOC), superior paraolivary nucleus, medial nucleus of the trapezoid body (MNTB), ventrolateral lemniscus, and central nucleus of the inferior colliculus (CIC). In the VCN and CIC, NB-2 was expressed in the regions that are known to respond to high frequencies. In situ hybridization combined with immunohistochemistry suggested that NB-2 is expressed only in neurons. NB-2 was colocalized with glutamatergic elements in the neuropil and the calyces of Held but not with glycinergic or GABAergic elements. NB-2 expression in the SOC was first detected at embryonic day (E)19, reached a maximum level at postnatal day (P)7, and declined thereafter. Immunolabeling with VGLUT1 and VGLUT2, markers for mature and premature glutamatergic synapses, respectively, in combination with NB-2 immunolabeling revealed that NB-2 is expressed at glutamatergic synapses. Collectively, our findings suggest that NB-2 plays a key role in maturation of glutamatergic synapses in the brainstem during the final stages of auditory development.

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Section: Nb-2 Expression Is Transient In the Soc And Just Precedes Thmentioning

confidence: 96%

Preferential localization of neural cell recognition molecule NB‐2 in developing glutamatergic neurons in the rat auditory brainstem

Toyoshima

Sakurai

Shimazaki

et al. 2009

J of Comparative Neurology

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“…In that study, focal electroporation revealed that EphA4 is most likely operating in a reverse signaling mode, in which Eph receptors signal through ephrins, and may attract NM axons. A likely binding partner for EphA4 is ephrin-B2, which is expressed on NM axons (Cramer et al, 2002(Cramer et al, , 2006. While ephrin-B2 appears to be expressed uniformly throughout NM, it is expressed in a tonotopic gradient in the glial margin ventral to NL (Person et al, 2004).…”

Section: Eph Protein Interactions In the Auditory Brainstemmentioning

confidence: 98%

“…Several Eph proteins are expressed in the auditory brainstem during development (Cramer et al, 2000b(Cramer et al, , 2002Person et al, 2004;Cramer, 2005). The Eph receptor EphA4 is strongly expressed in the dorsal neuropil and in the cell bodies of NL at chick embryonic day 10 (E10), when synaptic connections form.…”

Section: Introductionmentioning

confidence: 99%

EphA4 misexpression alters tonotopic projections in the auditory brainstem

Huffman

Cramer

2007

Developmental Neurobiology

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Auditory pathways contain orderly representations of frequency selectivity, which begin at the cochlea and are transmitted to the brainstem via topographically ordered axonal pathways. The mechanisms that establish these tonotopic maps are not known. Eph receptor tyrosine kinases and their ligands, the ephrins, have a demonstrated role in establishing topographic projections elsewhere in the brain, including the visual pathway. Here, we have examined the function of these proteins in the formation of auditory frequency maps. In birds, the first central auditory nucleus, n. magnocellularis (NM), projects tonotopically to n. laminaris (NL) on both sides of the brain. We previously showed that the Eph receptor EphA4 is expressed in a tonotopic gradient in the chick NL, with higher frequency regions showing greater expression than lower frequency regions. Here we misexpressed EphA4 in the developing auditory brainstem from embryonic day 2 (E2) through E10, when NM axons make synaptic contact with NL. We then evaluated topography along the frequency axis using both anterograde and retrograde labeling in both the ipsilateral and contralateral NM-NL pathways. We found that after misexpression, NM regions project to a significantly broader proportion of NL than in control embryos, and that both the ipsilateral map and the contralateral map show this increased divergence. These results support a role for EphA4 in establishing tonotopic projections in the auditory system, and further suggest a general role for Eph family proteins in establishing topographic maps in the nervous system.

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“…Eph/Ephrin signaling is known to play an important role in the establishment of auditory brainstem circuits, including midline patterning effects (Cramer et al, 2002(Cramer et al, , 2006. In contrast, only one study to date has examined the importance of the midline guidance factors, netrin-1, DCC, slit, and robo, in the formation of auditory brainThe Journal of Comparative Neurology.…”

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confidence: 94%

Molecular guidance cues necessary for axon pathfinding from the ventral cochlear nucleus

Howell

Morgan

Jarjour

et al. 2007

J of Comparative Neurology

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During development, multiple guidance cues direct the formation of appropriate synaptic connections. Factors that guide developing axons are known for various pathways throughout the mammalian brain; however, signals necessary to establish auditory connections are largely unknown. In the auditory brainstem the neurons whose axons traverse the midline in the ventral acoustic stria (VAS) are primarily located in the ventral cochlear nucleus (VCN) and project bilaterally to the superior olivary complex (SOC). The circumferential trajectory taken by developing VCN axons is similar to that of growing axons of spinal commissural neurons. Therefore, we reasoned that netrin-DCC and slit-robo signaling systems function in the guidance of VCN axons. VCN neurons express the transcription factor, mafB, as early as embryonic day (E) 13.5, thereby identifying the embryonic VCN for these studies. VCN axons extend toward the midline as early as E13, with many axons crossing by E14.5. During this time, netrin-1 and slit-1 RNAs are expressed at the brainstem midline. Additionally, neurons within the VCN express RNA for DCC, robo-1, and robo-2, and axons in the VAS are immunoreactive for DCC. VCN axons do not reach the midline of the brainstem in mice mutant for either the netrin-1 or DCC gene. VCN axons extend in pups lacking netrin-1, but most DCC-mutant samples lack VCN axonal outgrowth. Stereological cell estimates indicate only a modest reduction of VCN neurons in DCC-mutant mice. Taken together, these data show that a functional netrin-DCC signaling system is required for establishing proper VCN axonal projections in the auditory brainstem.

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Expression of EphB receptors and EphrinB ligands in the developing chick auditory brainstem

Cited by 37 publications

References 149 publications

Preferential localization of neural cell recognition molecule NB‐2 in developing glutamatergic neurons in the rat auditory brainstem

Preferential localization of neural cell recognition molecule NB‐2 in developing glutamatergic neurons in the rat auditory brainstem

EphA4 misexpression alters tonotopic projections in the auditory brainstem

Molecular guidance cues necessary for axon pathfinding from the ventral cochlear nucleus

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