GDNF reseptorin GFRa1 rooli hiiren koklean spiraaligangliohermosolujen kehityksessä ja ylläpidossa.

The sound stimulus sensed in cochlea by hair cells and is then transmitted from sensory hair cells by spiral ganglion neurons. The development of spiral ganglion neurons is dependent on different neurotrophic factors, and they have also been shown to support and protect these neurons in mature cochlea. GDNF has been detected in cochlea over 20 years ago, but still there is no consensus how it is operating in cochlea, although its protective effect against noise damage has been shown in many studies. GDNF signals through its receptor’s tyrosine kinase RET and cell surface protein GFRa1. GDNF has been detected in hair cells and GFRa1 in spiral ganglion neurons by in situ hybridization, but RET expression was not detected in this study. RET-independent GDNF signalling through GFRa1 has been shown operating in developmental processes in neurons and GDNF is upregulated as a result of noise exposure, and RET-independent signalling could be the mechanism via GDNF protects the SNGs. The aim of this thesis is to study RET-independent signalling in cochlea by preventing GFRa1 expression without pathological conditions. Transgenic mice were generated, and their cochlear phenotypes were analysed. Since gfra1 expression pattern varies with age, the loss of gfra1 both developing and mature cochlea. Results imply that GFRa1 seems not to have role in development of innervation, hearing function nor maintenance of mature neurons, but this could not be fully confirmed in this thesis. Thus, RET-independent signalling does not seem to have a role in spiral ganglion neurons. The mechanism of GDNF signalling in pathological condition remains to be solved in future studies.