The long-term goal of this research is to understand how stable differences in developmental ability are established in the neural crest (NC) cell lineage of vertebrate embryos. When trunk NC cells segregate from neural tube epithelium in vivo, they enter a cell- free, extracellular matrix-rich """"""""migration staging area"""""""" (MSA), and then disperse on two distinct migration pathways. Trunk NC cells that disperse early on a medioventral (""""""""medial"""""""") pathway between the neural tube and the somites give rise to both neuronal and non-neuronal derivatives. These include sensory, autonomic and enteric neurons, and Schwann sheath cells and glia of the peripheral ganglia. In contrast, trunk NC cells that disperse lateron a dorsolateral (""""""""lateral"""""""") pathway never give rise to neuronal derivatives. The principal investigator has learned that developmentally-distinct subpopulations of crest-derived cells are present early in migrating crest populations. One of these subpopulations--neurogenic precursors--appears transiently among the earliest premigratory cells. Neurogenic precursors transiently require trophic support for survival. They appear to disperse exclusively on the medial migration pathway, and ultimately give rise to a variety of neuronal phenotypes in peripheral ganglia. In the next grant period, the principal investigator will test the hypothesis that developmental cues in the embryonic environment selectively regulate survival, dispersal, and differentiation of specified neurogenic precursors. In addition, the principal investigator will characterize the molecular mechanisms involved in regulating the segregation and fate of these neurogenic precursors in the crest lineage. Specifically, the principal investigator proposes: (1) to combine cell- lineage analysis and neuron-specific molecular markers to characterize the initial segregation of neurogenic precursors in the neural crest lineage; (2) to examine the role of specific environmental cues (retinoic acid, NT-3, and BDNF) and their receptors in the segregation and subsequent survival of crest-derived neurogenic precursors; (3) to assess the function of members of the neuron-specific (Hu) family of RNA-binding proteins in neuronal differentiation by examining the consequences of Hu misexpression in neural crest-derived cells; and (4) to identify early molecular markers of neuronal specification and differentiation in neural crest-derived neurogenic precursors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS029438-07S1
Application #
6152142
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Finkelstein, Robert
Project Start
1991-08-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2001-04-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Oregon
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
Wakamatsu, Yoshio; Endo, Yukinori; Osumi, Noriko et al. (2004) Multiple roles of Sox2, an HMG-box transcription factor in avian neural crest development. Dev Dyn 229:74-86
Weston, James A; Yoshida, Hisahiro; Robinson, Victoria et al. (2004) Neural crest and the origin of ectomesenchyme: neural fold heterogeneity suggests an alternative hypothesis. Dev Dyn 229:118-30
Wakamatsu, Yoshio; Osumi, Noriko; Weston, James A (2004) Expression of a novel secreted factor, Seraf indicates an early segregation of Schwann cell precursors from neural crest during avian development. Dev Biol 268:162-73
Wakamatsu, Y; Maynard, T M; Weston, J A (2000) Fate determination of neural crest cells by NOTCH-mediated lateral inhibition and asymmetrical cell division during gangliogenesis. Development 127:2811-21
Henion, P D; Blyss, G K; Luo, R et al. (2000) Avian transitin expression mirrors glial cell fate restrictions during neural crest development. Dev Dyn 218:150-9
Maynard, T M; Wakamatsu, Y; Weston, J A (2000) Cell interactions within nascent neural crest cell populations transiently promote death of neurogenic precursors. Development 127:4561-72
Wakamatsu, Y; Maynard, T M; Jones, S U et al. (1999) NUMB localizes in the basal cortex of mitotic avian neuroepithelial cells and modulates neuronal differentiation by binding to NOTCH-1. Neuron 23:71-81
Weston, J A (1998) Lineage commitment and fate of neural crest-derived neurogenic cells. Adv Pharmacol 42:887-91
Wakamatsu, Y; Weston, J A (1997) Sequential expression and role of Hu RNA-binding proteins during neurogenesis. Development 124:3449-60
Henion, P D; Weston, J A (1997) Timing and pattern of cell fate restrictions in the neural crest lineage. Development 124:4351-9

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