The neural crest is a transient population of cells, named because it arises on the """"""""crest"""""""" of the closing neural tube. Neural crest cells emigrate from the neural tube, migrate along precise pathways and finally localize in characteristic sites in the embryo to form the ganglia of the peripheral nervous system, as well as melanocytes and the craniofacial skeleton. They form the autonomic nervous system that innervates numerous organs such as the gut, kidneys and pancreas. Correct migration to and innervation of these targets is essential for proper body function and homeostasis. During the previous grant period, we showed that the dominant guidance cues for neural crest migration may be inhibitory: interactions between Eph receptors on neural crest cells and ephrins in the caudal somite results in a segmentally restricted migratory pattern in the trunk. In addition, Slit chemorepellants expressed prevent trunk neural crest cells from invading the gut (deBellard et al., 2003). Using a genomics approach, we have analyzed the repertoire of genes expressed by premigratory neural crest cells. This has provided us with numerous new candidate genes that may function in the migratory process. Genes identified in neural folds include Slit, laminin a5, as well as a novel chemokine. The proposed experiments will characterize the function of these candidate genes in regulating important events in neural crest migration and other developmental processes. We will use both in vivo and in vitro experiments combining gain-of-function and loss-of-function approaches to examine: 1. The role of the dual inhibitory and migration-stimulating activity of Slit in the migration of trunk and cranial neural crest cells. 2. The function of the a5 subunit of laminin in early neural crest development. 3. The function of a novel chemokine in neural crest migration. 4. The function of this novel chemokine in limb development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051051-23
Application #
6925520
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Gwinn, Katrina
Project Start
1981-07-01
Project End
2008-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
23
Fiscal Year
2005
Total Cost
$374,625
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Gammill, Laura S; Gonzalez, Constanza; Bronner-Fraser, Marianne (2007) Neuropilin 2/semaphorin 3F signaling is essential for cranial neural crest migration and trigeminal ganglion condensation. Dev Neurobiol 67:47-56
Epperlein, Hans-Henning; Selleck, Mark A J; Meulemans, Daniel et al. (2007) Migratory patterns and developmental potential of trunk neural crest cells in the axolotl embryo. Dev Dyn 236:389-403
Gammill, Laura S; Gonzalez, Constanza; Gu, Chenghua et al. (2006) Guidance of trunk neural crest migration requires neuropilin 2/semaphorin 3F signaling. Development 133:99-106
Coles, Edward G; Gammill, Laura S; Miner, Jeffrey H et al. (2006) Abnormalities in neural crest cell migration in laminin alpha5 mutant mice. Dev Biol 289:218-28
Taneyhill, Lisa A; Bronner-Fraser, Marianne (2005) Recycling signals in the neural crest. J Biol 4:10