Sensory neurons : Stem cells and development

Sammanfattning: The sensory nervous system is the only means we have of communicating with the surrounding world. The neurons responsible for the sensation of pain, touch, the ability to know the position of our limbs and part of maintenance of body posture are located in the dorsal root ganglia (DRG). Stem cell biology has, during the recent years greatly enhanced our understanding of developmental processes. The aim of this thesis was to isolate and characterize stem cells from the sensory nervous system and to study the development of functional neuronal subtypes. In the work presented 1 show the identification of a neural crest stem cell (NCSC) that is located in the boundary cap (BC). The BC is a transient structure present during embryogenesis lining the boundary between the peripheral and central nervous system at the exit/entry zone of sensory and motor efferents. This multipotent stem cell is unique as compared to previously described NCSCs, in its ability to form sensory neurons in vitro. The sensory neurons are functionally active as assayed by calcium imaging using temperature stimuli and sensory specific transient receptor potential (TRP)-channel ligands. 1 further show that the boundary cap neural crest stem cell (bNCSC) can give rise to Schwann cells that myclinate regenerating axons in vivo, suggesting a possibility for the use of these stem cells for regenerative therapy. The bNCSC express the well described stem cell marker, stage specific antigen 1 (SSEA-1) as well as proteins involved in the production of gamma amino butyric acid (GABA). Furthermore, GABA drastically reduces the proliferation of bNCSC, in a pathway independent of intracellular signalling. Antagonizing endogenous production using GABAA receptor antagonist bicuculline increases the same. This suggests GABA as a signal to regulate proliferation in the BC stem cell niche and thus providing the basis for a possible increase of production in response to an injury. In the last part of the thesis 1 describe and define the developmental emergence of different subtypes of developing sensory neurons based on functional responses to capsaicin, menthol, and cinnamon aldehyde, agonists to TRPV1, TRPM8 and TRPA 1 respectively.