Explaining certain human limb anomalies and the limb-hematopoiesis community of syndromes using a model of determination.
Disturbances of determination, the process of limitation of developmental potential, can cause structural as well as histologic anomalies. A polar coordinate model (PCM) developed from studies in animals, in which determination depends upon positional information arranged along polar coordinates, can be used to explain certain classes of human limb anomalies. Under the model, interference with this system primarily affects distal patterning. If the radial area is distal to the zone of polarizing activity in embryological development, as it appears to be, the PCM explains the teratologic equivalence of preaxial duplications and deficiencies in certain circumstances and the prevalence of ulnar dimelias in forearm duplications. Also, failures of hematopoiesis can be considered late problems with determination and may be markers for abnormalities of a determinative process that also has earlier developmental consequences. Abnormalities of retinoic acid morphogen receptors would be one possible mechanism. This would provide a rationale for the known association of postnatal hematologic problems with developmental anomalies preferentially affecting the radial area. Syndromes with limb and hematopoietic problems may well be a community of determinative disorders.
Lubinsky
M S
MS
Division of Genetics, Children's Hospital of Wisconsin, Milwaukee 53201.
D000015:Abnormalities, Multiple / Q000196:embryology; D005542:Forearm / Q000002:abnormalities* / Q000196:embryology; D006410:Hematopoiesis; D006801:Humans; D008954:Models, Biological; D013577:Syndrome