The neutral crest is a population of migratory cells that arise from the ectoderm of vertebrate embryos and give rise to a diverse range of cell types, including most of the peripheral nervous system, melanocytes and the craniofacial skeleton. It has been classically assumed that the neutral crest is a segregated population in the early ectoderm, lying between the neutral plate and presumptive epidermis. However, our recent studies on avian embryos show that individual precursor cells within the """"""""neutral folds"""""""" can form neutral tube (central nervous system), neutral crest (peripheral nervous system) and epidermal derivatives. This led us to explore the interactions that impart the potential form the neural crest. Interestingly, we found that neural crest cells are generated when epidermis and neural plate are juxtaposed-a classic type of embryonic induction. The proposed experiments aim to characterize this inductive interaction that leads to neural crest formation and to examine the plasticity of early ectodermal derivatives. To continue our studies on the mechanisms responsible for genesis of the neural crest, we will further characterize the molecular nature of the inductive interaction and will test the function of some candidate inducers in vivo and in vitro. We will examine the ability of ventralizing signals to compete with induction of the neural crest, using both grafting and ectopic expression paradigms. Finally, we will examine the lineage relationships and plasticity between neural crest cells and other ectodermal derivatives by challenging their prospective fates via transplantation. Much of the experimental design will involve in vivo experimental manipulations coupled with cell marking techniques, molecular biological approaches, as well as in situ hybridization to examine patterns of gene expression. Specific experiments will: 1. Characterize the molecular nature of the inductive interaction underlying neural crest formation. 2. Determine the ability of ventralizing signals to repress neural crest formation. 3. Determine the competence of ectoderm and neural plate to assume a neural crest fate. 4. Determine the competence of neural crest cells to assume a neural tube fate after transplantation into the ventral neural tube.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS036585-01A1
Application #
2624935
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Small, Judy A
Project Start
1998-04-01
Project End
2002-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Ezin, Akouavi M; Fraser, Scott E; Bronner-Fraser, Marianne (2009) Fate map and morphogenesis of presumptive neural crest and dorsal neural tube. Dev Biol 330:221-36
Coles, Edward G; Lawlor, Elizabeth R; Bronner-Fraser, Marianne (2008) EWS-FLI1 causes neuroepithelial defects and abrogates emigration of neural crest stem cells. Stem Cells 26:2237-44
Adams, Meghan S; Gammill, Laura S; Bronner-Fraser, Marianne (2008) Discovery of transcription factors and other candidate regulators of neural crest development. Dev Dyn 237:1021-33
Sauka-Spengler, Tatjana; Bronner-Fraser, Marianne (2008) A gene regulatory network orchestrates neural crest formation. Nat Rev Mol Cell Biol 9:557-68
Taneyhill, Lisa A; Coles, Edward G; Bronner-Fraser, Marianne (2007) Snail2 directly represses cadherin6B during epithelial-to-mesenchymal transitions of the neural crest. Development 134:1481-90
Coles, E G; Taneyhill, L A; Bronner-Fraser, M (2007) A critical role for Cadherin6B in regulating avian neural crest emigration. Dev Biol 312:533-44

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