This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Neural tube defects are amongst the most common birth defects, occurring with a frequency of 1 in 1000 births. Although nearly 100 single gene mutations have been documented in animal models to cause neural tube defects, few if any of these gene mutations have been characterized at a cellular and/or molecular level. It has been demonstrated that mutation in the gene encoding the protein c-ski (a regulator of gene transcription) in mice causes neural tube defects. Studies proposed within the present application will attempt to elucidate the cellular and molecular basis of c-ski gene inactivation in the genesis of neural tube defects. The hypothesis to be examined is that during the genesis of NTDs, the cranial neural crest is a highly susceptible cellular target of c-ski loss of function. Loss of c-ski function as a transcriptional regulator may result in significant alterations in neural crest gene expression that will be assessed by microarray based molecular profiling of isolated neural crest cells. Attendant perturbations in neural crest formation, migration, proliferation or neural crest cell death will be examined in a unique animal model system that offers the ability to track the functional consequences of c-ski gene deletion (mutation) in labeled neural crest cells in intact animals. The studies proposed in the current application offer a novel approach to address genetic differences in susceptibility to NTDs, as well as serve to initiate investigation, at a mechanistic level, of potential cellular and molecular targets of Ski during cranial neural tube morphogenesis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017702-05
Application #
7381925
Study Section
Special Emphasis Panel (ZRR1-RI-A (02))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
5
Fiscal Year
2006
Total Cost
$43,905
Indirect Cost
Name
University of Louisville
Department
Dentistry
Type
Schools of Dentistry
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
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