Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification

Significance While knowledge of signaling mechanisms orchestrating the development and diversification of peripheral somatosensory neurons is extensive, our understanding of the mechanisms controlling chemosensory neuron specification remains rudimentary. Lingually projecting sensory neurons of the geniculate ganglion are receptive to the five taste qualities, as well as temperature and tactile stimuli, but the mechanisms responsible for the diversification of the unique subpopulations that respond to one, or several, of these stimuli remain unknown. Here we demonstrate that the GDNF-Ret signaling pathway exerts a unique, dual function in peripheral taste system development and postnatal function. Ret acts embryonically to regulate the expression of the chemosensory master regulator Phox2b, thus inducing chemosensory differentiation, while postnatally acting to specify a molecularly unique subpopulation of lingual mechanoreceptors.