The neural crest is a heterogeneous population of progenitors that migrates from the dorsal neural tube and gives rise to the sensory and autonomic neurons and gila of the peripheral nervous system. Among the migrating progenitors are neural crest stem cells (NCSCs), which are defined based on their ability to self-renew and their ability to undergo multilineage differentiation, forming neurons, gila, and myofibroblasts. However, little is known about when, where, and how NCSCs undergo restrictions to a sensory or autonomic lineage. Some studies have suggest that neural crest progenitors become restricted at the onset of migration from the neural tube such that they can only give rise to either sensory and autonomic neuronal subtype, and that migrating and post migratory NCSCs specifically are unable to give rise to sensory neurons. However, other studies have suggested that at least some single cells in the emigrating population of neural crest cells retain the ability to generate both sensory and autonomic neurons in vivo. Moreover, I have recently discovered that the fetal dorsal root (sensory) ganglion (DRG) contains a population of multipotent progenitors that can form sensory neurons in culture and that these cells may persist in postnatal DRG. These observations raise the question of whether a population of NCSCs with both sensory and autonomic potential persists in developing and postnatal DRG. The persistence of multipotent progenitors in the postnatal DRG also raises the question of whether these progenitors are transformed by neurofibromin 1 (NF1) deficiency to form plexiform neurofibromas containing neurons, gila, and myofibroblasts. To address these questions, I propose to first purify and characterize the multipotent progenitors within embryonic and postnatal DRG and then study the effect of NF1 deficiency on these cells. I hope to gain important new insights into the regulation of NCSC fate determination, the role of stem cells in PNS development, and the etiology of neurofibromatosis.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Special Emphasis Panel (ZNS1-SRB-M (06))
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Finkelstein, Robert
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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Joseph, Nancy M; He, Shenghui; Quintana, Elsa et al. (2011) Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut. J Clin Invest 121:3398-411
Joseph, Nancy M; Mosher, Jack T; Buchstaller, Johanna et al. (2008) The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell 13:129-40