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A better understanding of hearing loss
3/22/13

Repulsion for better connection

To explore their theory of chemorepulsion, Jean Defourny and Brigitte Malgrange decided to examine the expression pattern for two types of proteins: Ephrins and their receptors (Ephs).  "There are about twenty Ephrins and half as many Eph receptors. We focused on proteins that had a complementary expression pattern in the inner ear. That is, the ones which express Ephrin in the outer hair cells and have receptors in the type I spiral ganglion neurons," states Brigitte Malgrange. That's how they realized that Ephrin-A5 is exclusively expressed in outer hair cells while its cognate EphA4 receptor is located specifically in the type I neurons. "When the Ephrin-A5 binds to the EphA4 receptor, this creates a repulsion of the type I neuron projections," says the researcher. These results, published in the journal Nature Communications (1), were the first to demonstrate the chemorepulsion of neurites by Ephrins in the inner ear. 

The researchers tested their initial hypothesis through a series of experiments and in particular through the use of mice which had both proteins removed.  "One group of mice didn't express Ephrin-A5 and the other group didn't have any EphA4. In both cases our hypothesis proved to be accurate," said Brigitte Malgrange.

A new avenue for hearing restoration

(EN)-image-confocale-E15.5While this discovery is still in the fundamental research stage, in the long term it could lead to therapies to restore hearing in people affected by hearing loss. "If we understand how auditory function develops, we can try to restore connections between the hair cells and the spiral ganglion neurons. Thanks to our research, we now know how it's possible to prevent type I neurons from connecting to outer hair cells," explains the director of the GIGA-neurosciences research unit.

In the near future, Brigitte Malgrange and her team would like to better understand what happens in the actual hair cell-neuron connections. "Here we have shown on a rough scale that when we remove the Ephrin A5 or EphA4 proteins, mice have significant hearing problems.  Now we would like to analyse what happens directly in the inner hair cell in regards to neurotransmission," says the scientist. During neurotransmission, the hair cells release a neurotransmitter, glutamate, which binds to the receptors located on the neuron projections. "We would like to see if the absence of Ephrin-A5 or Eph4 directly affects this neurotransmission," states Brigitte Malgrange. Furthermore, she would also like to investigate whether other molecules known to have repulsion properties could also play a role in the establishment of hair cell-spiral ganglion neuron connections.

(1) Defourny J, Poirrier AL, Lallemend F, Mateo Sánchez S, Neef J, Vanderhaeghen P, Soriano E, Peuckert C, Kullander K, Fritzsch B, Nguyen L, Moonen G, Moser T, Malgrange "B. Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells." Nat Commun 2013 Feb 5.:1438.

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