Lewin Lab

Henning Frenzel, Regina Hartl, Stefan Lechner, Nevena Milenkovic, Simone Pifferi

Hereditary deafness is a relatively common phenomenon and a large number of genes have been identified that when mutated lead to deafness in mouse and man. We are working with several deaf mutant mice to examine whether genes required for normal mechanotransduction in the inner ear may also be required for normal cutaneous sensation. Our data indicate that members of the unconventional myosin protein family have a common function in sensory neurons and in hair cells, mechanotransducing cells of the inner ear. In both cell types these proteins may function to regulate the adaptation of the mechanotransduction channels. We are currently working on further hearing genes that may also affect cutaneous mechanosensation. The same genes as we study in the mouse are also mutated in humans and it is possible that the perception of cutaneous touch stimuli is altered in such patients. We are measuring pyschometric functions in normals and hearing impaired people in order to describe quantitatively differences in the perception of touch. We are also carrying out a large twin study, to examine the heritability of touch acuity in humans. Initial results suggest that genetic factors are very important in determining how good our sense of touch is. We are also pursuing the hypothesis that some of the genetic factors influencing touch may also directly affect the second mechanosensory sense, hearing.

We have been interested in the development of mechanosensation for many years and it was remarkable how little was known in this area. We have recently shown, in a very detailed study, that sensory neurons acquire their competence to detect mechanical stimuli very early in embryonic development. Interestingly, very distinct developmental mechanisms are used to induce such competence in neurons that underlie touch sensation as opposed to nociception (painful stimuli). For example, we have shown that NGF plays a critical role in the acquisition of transduction competence by nociceptors.

Selected publications

1. Lechner, S.G., Frenzel, H., Wang, R. & Lewin, G.R. Developmental waves of mechanosensitivity acquisition in sensory neuron subtypes during embryonic development. The EMBO journal 28, 1479-91 (2009).