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23/5/2014

CEXS-UPF: The grid of audition: the ordered organisation of hair cells in the ear

CEXS-UPF: The grid of audition: the ordered organisation of hair cells in the ear


News from CEXS-UPF


In a recent paper, two groups, from the Universitat Pompeu Fabra and the Universitat de Barcelona, use experimental and computational methods to investigate how the interaction between two genes, Atoh1 and Notch, determine the fate of hair cells and their precise spatial organisation.

The work shows that the organisation of hair cells generated by Atoh1 is extraordinary robust. Aided by computational modeling, the authors propose that this is dependent on the ability of Atoh1 to promote its own expression - its autoactivation - and on the interaction with Notch. Atoh1 behaves as a master gene that drives hair cell development, however, not all cells expressing Atoh1 differentiate into hair cells.

Most defects in human audition, like those caused by sound damage, toxics or hereditary defects, are caused by the loss of hair cells. Unlike other vertebrates, like the chick, hair cells do not regenerate after damage in mammals. However, some recent results have tantalized the field by showing that the blockade of the activity of the Notch protein favours the regeneration of hair cells in mammals. Many scientists believe that deciphering the developmental mechanisms that operate in the embryo will provide clues for better designing strategies for tissue regeneration. The results found in the work of Petrovic et al. give new insights into the interaction between Atoh1, Notch and Notch ligands that can help understand how hair cells can regenerate in orderly patterns and hence, to restore proper function.

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Reference:
Petrovic J, Formosa-Jordan P, Luna-Escalante JC, Abelló G, Ibañes M, Neves J, Giraldez F; Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear. Development. 2014 May 12