Peripheral neural stem cells - maintenance in peripheral ganglia and nerves

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We use the neural crest as a model system to study the biology of vertebrate neural stem cells. Stem cells are present in neural crest and in neural crest-derived peripheral ganglia and nerves. Peripheral nerve stem cells (called here PNSCs) were induced to differentiate in vivo to noradrenergic sympathetic neurons in response to differentiation factors (BMPs) and transcription factors (Cash1, Phox2a, Phox2b, dHand) involved in autonomic neuron development. The neurogenin bHLH transcription factors directed the differentiation to sensory neurons. However, the number of cells generated was small and the PNSCs were identified retrospectively by the differentiation of their progeny. Recently, PNSCs were prospectively isolated and were shown to be self-renewing and to give rise to neuronal and glial cells in clonal cultures. However, when isolated PNSCs were transplanted into the PNS of host embryos they gave rise to neurons that did neither express noradrenergic nor sensory properties. This project aims to overcome this restriction and to elicit the generation of noradrenergic and sensory neurons from isolated PNSCs. We propose to develop stem cell culture conditions for PNSCs, to analyse the developmental potential of PNSCs in vitro and by transplantation into early host embryos. We will investigate the effect of stem cell propagation in culture on the potential to develop noradrenergic and sensory neuronal fates in vivo and to express specific transcription factors in immunoselected, cultured PNSCs to induce the generation of noradrenergic and sensory neurons.