Gdnf Family Receptors in Peripheral Target Innervation and Hormone Production

..................................................................................................................8 REVIEW OF THE LITERATURE ...............................................................................9 Introduction....................................................................................................................9 Glial cell line-derived neurotrophic factor family .........................................................9 GDNF family ligands.................................................................................................9 GDNF family receptors............................................................................................12 RET-dependent GDNF family signalling ................................................................14 RET-independent GDNF family signalling .............................................................18 Derivatives of the neural crest: peripheral nervous system and neuroendocrine cells 19 Somatic sensory nervous system .............................................................................20 Sympathetic nervous system and the adrenal gland ................................................24 Parasympathetic nervous system .............................................................................26 Enteric nervous system ............................................................................................27 Thyroid C-cells ........................................................................................................29 In vivo functions of GDNF family factors ...................................................................30 GDNF/GFRα1/Ret signalling in the development of the enteric and parasympathetic nervous systems ............................................................................31 GDNF/GFRα1/Ret signalling outside the nervous system......................................32 NRTN/GFRα2 signalling in the development of the parasympathetic and enteric neurons.....................................................................................................................33 GFRα3/ARTN signalling in the migration and initial axon outgrowth of sympathetic neurons.................................................................................................34 PSPN may protect the brain from ischaemia ...........................................................35 RET mutations in human diseases ...........................................................................35 AIMS OF THE STUDY ..............................................................................................37 MATERIALS AND METHODS.................................................................................38 RESULTS AND DISCUSSION..................................................................................41 A. GFRα2 in peripheral neurons..................................................................................41 The development of intrapancreatic ganglia requires GFRα2 .................................41 GFRα2 is needed to maintain the cell size of cholinergic sympathetic neurons .....42 GFRα2 is required to maintain the cell size of IB4-positive sensory neurons .........43 B. GFRα2 in peripheral innervation ............................................................................44