Neural tube defects are amongst the most common of all birth defects in humans, affecting approximately 1 in 1,000 live born infants. These malformations, which include spina bifida, anencephaly and meningomyeloceles, represents the single largest group of etiologies for patients with mental deficiency. In spite of the common nature of these congenital defects, efforts to obtain a clear understanding of their pathogenesis on a molecular level have been limited by the availability of sufficient quantities of embryonic material from which to isolate mRNA and ultimately develop cDNA libraries to screen. The research program described in this proposal takes advantage of two recent advances in molecular biological techniques that can overcome this problem. Using in situ transcription (IST) and anti-sense RNA (aRNA) amplification, we intend to examine in murine embryos the composite changes in a population of mRNAs from selected candidate genes whose function is believed to be critical for normal neural tube morphogenesis. The experimental paradigm will focus on the curly tail (ct) mutant, but it will also include embryos bearing a genetic mutation at the Splotch locus (Sp), which confers spontaneous anterior and/or posterior neural tube defects in homozygous embryos. These experiments should provide new data on gene expression during the period of neural tube closure in embryos with neural tube defects. Utilizing a differential hybridization screening strategy, it will be possible to isolate those sequences that are vastly enriched or in very low abundance yet remain of critical important in the pathogenesis of neural tube defects. It will also be possible to determine whether anterior and posterior defects are mechanistically unique, or if they merely represent regional differences of the same malformation. The results obtained in these murine models will provide insight into the development of analogous defects in humans, which may lead to better preventative measures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES007165-01
Application #
2156350
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1994-07-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845