The entirety of the craniofacial skeleton arises from the cranial neural crest, a migratory cell type that forms in the central nervous system, migrates extensively and differentiates into the cartilage and bone of the face.
The aim of this proposal is to identify and functionally characterize genes expressed in the cranial neural crest in order to better understand the molecular regulation of craniofacial development. My preliminary results have described a gene expression profile of a premigratory neural crest cell and have identified candidate regulatory molecules involved in craniofacial patterning. In the first phase of the award, the function of two of these genes that are strongly expressed in developing cranial neural crest will be analyzed in detail, and a screen will be carried out to identify new genes expressed during neural crest migration. The role of the receptor neuropilin-2 and its ligands in the cranial neural crest will be analyzed using in vivo and vitro approaches in chicken embryos and in mice bearing neuropilin-2 null mutations. Concomitanity, a gene with no known homology that is highly specific to neural crest precursors will be functionally characterized in chick cranial neural crest by gain-and loss of function techniques. Genes expressed during cranial neural crest migration will be identified in a genome-scale array screen. In the second phase of the award, the function of additional genes will be analyzed through traditional approaches (chick overpression and creation of the mouse mutants) in addition to the proposed construction of a neural crest-specific array that can be used to probe gene expression during cranial neural crest development under different conditions. The Scholar Development Phase of this award will be carried out in the lab of Dr. Marianne Bronner-Fraser at Caltech, a leader in the field of neural crest research at one of the most highly regarded research universities in the country. The candidate, Dr. Laura Gammill, has been a postdoctoral scholar in Dr. Bronner-Fraser's lab since 1999. The candidate's effort thus far has been to create a unique macroarray reagent that was used to identify a large collection of genes involved in early neural crest development. The immediate career goal is to develop research expertise in the area of chick and mouse embryology and to practice mentoring skills so as to obtain an academic faculty position. The long-term career goal is to run a laboratory doing basic research in neural crest and craniofacial development. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Career Transition Award (K22)
Project #
7K22DE015309-05
Application #
7324450
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2003-09-01
Project End
2009-05-31
Budget Start
2007-03-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$1
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Fairchild, Corinne L; Conway, Joseph P; Schiffmacher, Andrew T et al. (2014) FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation. Mech Dev 132:1-12
Fairchild, Corinne L; Gammill, Laura S (2013) Tetraspanin18 is a FoxD3-responsive antagonist of cranial neural crest epithelial-to-mesenchymal transition that maintains cadherin-6B protein. J Cell Sci 126:1464-76
Roffers-Agarwal, Julaine; Hutt, Karla J; Gammill, Laura S (2012) Paladin is an antiphosphatase that regulates neural crest cell formation and migration. Dev Biol 371:180-90
Gammill, Laura S; Roffers-Agarwal, Julaine (2010) Division of labor during trunk neural crest development. Dev Biol 344:555-65
Roffers-Agarwal, Julaine; Gammill, Laura S (2009) Neuropilin receptors guide distinct phases of sensory and motor neuronal segmentation. Development 136:1879-88
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
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
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