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EphA4 provides repulsive signals to developing cochlear ganglion neurites mediated through ephrin-B2 and -B3


Brors, D; Bodmer, D; Pak, K; Aletsee, C; Schäfers, M; Dazert, S; Ryan, A F (2003). EphA4 provides repulsive signals to developing cochlear ganglion neurites mediated through ephrin-B2 and -B3. Journal of Comparative Neurology, 462(1):90-100.

Abstract

The ephrins and Eph receptors make up two large families of bi-directional signaling molecules that are known to play a role in the development of the nervous system. Recently, expression of EphA4 in the developing cochlea was shown, with strong expression in cells lining the osseous spiral lamina (OSL) through which afferent dendrites must pass to reach the organ of Corti (OC). It was also demonstrated that ephrin-B2 and -B3, both of which are known to interact with EphA4, are expressed by spiral ganglion (SG) neurons. To investigate the functional role of EphA4 in the development of inner ear neurons, neonatal rat SG explants were cultured for 72 hours on uniformly coated surfaces or near stripes of EphA4/IgG-Fc-chimera. Control explants were cultured on or near IgG-Fc and EphA1/IgG-Fc-chimera. To assess the roles of ephrin-B2 and -B3 in EphA4 signaling, SG explants were cultured with or without anti-ephrin-B2 and/or -B3 blocking antibodies. Growth patterns of SG neurites at the border of EphA4 receptor stripes showed repulsion, characterized by turning, stopping and/or reversal. In the case of IgG-Fc and EphA1, the neurites grew straight onto the stripes. Treatment with either anti-ephrin-B2 or -B3 blocking antibodies significantly reduced the repulsive effect of an EphA4 stripe. Moreover, when both antibodies were used together, neurites crossed onto EphA4 stripes with no evidence of repulsion. The results suggest that EphA4 provides repulsive signals to SG neurites in the developing cochlea, and that ephrin-B2 and -B3 together mediate this response.

The ephrins and Eph receptors make up two large families of bi-directional signaling molecules that are known to play a role in the development of the nervous system. Recently, expression of EphA4 in the developing cochlea was shown, with strong expression in cells lining the osseous spiral lamina (OSL) through which afferent dendrites must pass to reach the organ of Corti (OC). It was also demonstrated that ephrin-B2 and -B3, both of which are known to interact with EphA4, are expressed by spiral ganglion (SG) neurons. To investigate the functional role of EphA4 in the development of inner ear neurons, neonatal rat SG explants were cultured for 72 hours on uniformly coated surfaces or near stripes of EphA4/IgG-Fc-chimera. Control explants were cultured on or near IgG-Fc and EphA1/IgG-Fc-chimera. To assess the roles of ephrin-B2 and -B3 in EphA4 signaling, SG explants were cultured with or without anti-ephrin-B2 and/or -B3 blocking antibodies. Growth patterns of SG neurites at the border of EphA4 receptor stripes showed repulsion, characterized by turning, stopping and/or reversal. In the case of IgG-Fc and EphA1, the neurites grew straight onto the stripes. Treatment with either anti-ephrin-B2 or -B3 blocking antibodies significantly reduced the repulsive effect of an EphA4 stripe. Moreover, when both antibodies were used together, neurites crossed onto EphA4 stripes with no evidence of repulsion. The results suggest that EphA4 provides repulsive signals to SG neurites in the developing cochlea, and that ephrin-B2 and -B3 together mediate this response.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Otorhinolaryngology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:May 2003
Deposited On:26 Mar 2009 09:08
Last Modified:05 Apr 2016 12:43
Publisher:Wiley-Blackwell
ISSN:0021-9967
Publisher DOI:10.1002/cne.10707
PubMed ID:12761826
Permanent URL: http://doi.org/10.5167/uzh-8428

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