Carbon monoxide-induced axial skeletal dysmorphogenesis in the chick embryo.
BACKGROUND
Congenital axial skeletal defects affect two to three individuals per 1,000 live births. Without strong evidence for heritability, the cause is assumed to be multi-factorial. Carbon monoxide (CO), an increasingly prevalent environmental toxicant, is a potential environmental component in the etiology of these defects. The chick embryo is a useful model for the characterization and assessment of the mechanism(s) of action of basic developmental mechanisms.


METHODS
We have determined a critical period and dose for CO teratogenicity and established a model of CO-induced axial skeletal dysmorphogenesis in the chick embryo. The resulting phenotypes reveal a spectrum of axial skeletal defects ranging from minor defects of the vertebral canal and inter-vertebral discs, to thoraco-lumbar scoliosis, to a tailless phenotype reminiscent of caudal dysgenesis syndrome. These axial skeletal defects have been related to earlier developmental defects in somitogenesis, including errors in segmentation and epithehalization and the expression of the somitic epithelialization factor, Paraxis. We have examined patterns of cell death and apoptosis in CO exposed chick embryos to assess the target tissue(s) involved in the teratogenicity of CO.


RESULTS
With respect to the embryonic axis, the neural tube was found to be the most sensitive to CO-induced apoptosis, followed by the somitic mesoderm and Hensen's node.


CONCLUSIONS
We hypothesize that the somitic defects and the resulting axial skeletal dysmorphogenesis are caused by disrupted neural tube or ectoderm functions related to somite formation and maintenance. We also hypothesize that CO-induced dysmorphogenesis at this critical period of somitogenesis is caused by the overabundance of CO acting endogenously as a cellular signal, while coincidentally exerting its influence as a toxicant of oxygen delivery or utilization.
Alexander
Peter G
PG
Department of Orthopaedic Surgery and Graduate Program of Developmental Biology and Teratology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Tuan
Rocky S
RS
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D002248:Carbon Monoxide / Q000633:toxicity*; D002642:Chick Embryo; D008648:Mesoderm / Q000187:drug effects / Q000473:pathology; D009436:Neural Tube Defects / Q000209:etiology* / Q000473:pathology; D012886:Skull / Q000002:abnormalities* / Q000196:embryology; D019170:Somites / Q000187:drug effects / Q000473:pathology; D013131:Spine / Q000002:abnormalities* / Q000196:embryology
D002248:Carbon Monoxide