Conotruncal abnormalities represent profound disturbances of the basic architecture of the heart which occur in a significant numbeer of babies with congenital heart defects. Conotruncal abnormalities include persistent truncus arteriosus, transposition of the great vessels, tetralogy of Fallot and several other congenital heart malformations. The pathogenesis of conotruncal abnormalities is unknown. It has recently been discovered that occipital neural crest cells migrate into the conotruncus and that removal of these cells prior to their migration results in conotruncal malformation. This proposal will further define the extent of this migration and the role of neural crest cells in conotruncal development. Quail neural crest will be transplanted onto chick embryos at varying occipital levels. The quail cells will be mapped in the conotruncus to determine which levels of neural crest contribute to which areas of the conotruncal septum. Parts of occipital neural crest will be removed to determine whether specific lesions are associated with particular areas of neural crest. Various conotruncal teratogens will be studied with regard to their ability to disrupt occipital neural crest migration into the conotruncal region. This proposal represents a two-pronged advance in the area of conotruncal abnormalities in that it will result in a reliable model in which to study the morphogenesis of these abnormalities and it will advance our theories of the pathogenesis of this life-threatening congenital defect.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032546-02
Application #
3343902
Study Section
Cardiovascular Study Section (CVA)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
Phillips 3rd, M T; Waldo, K; Kirby, M L (1989) Neural crest ablation does not alter pulmonary vein development in the chick embryo. Anat Rec 223:292-8
Kirby, M L (1987) Cardiac morphogenesis--recent research advances. Pediatr Res 21:219-24
Nishibatake, M; Kirby, M L; Van Mierop, L H (1987) Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation. Circulation 75:255-64
Phillips, M T; Kirby, M L; Forbes, G (1987) Analysis of cranial neural crest distribution in the developing heart using quail-chick chimeras. Circ Res 60:27-30
Besson 3rd, W T; Kirby, M L; Van Mierop, L H et al. (1986) Effects of the size of lesions of the cardiac neural crest at various embryonic ages on incidence and type of cardiac defects. Circulation 73:360-4
Stewart, D E; Kirby, M L; Sulik, K K (1986) Hemodynamic changes in chick embryos precede heart defects after cardiac neural crest ablation. Circ Res 59:545-50
Kirby, M L; Turnage 3rd, K L; Hays, B M (1985) Characterization of conotruncal malformations following ablation of ""cardiac"" neural crest. Anat Rec 213:87-93