Notochordal-basichondrocranium relationships: abnormalities in experimental axial skeletal (dysraphic) disorders.

The notochordal-basichondrocranium relationships have been investigated in cranioschisis occulta with encephalocoele (CSO-EN) and in cranioschisis aperta with exencephaly (CSA-EX) which represent, respectively, a minimal and a severe form of experimentally induced axial skeletal (dysraphic) disorders. Although apparently different, these two malformations are considered to represent different degrees of the same basic abnormality (mesodermal insufficiency) which affects the paraxial mesoderm early in embryonic development. Three different experimental models (vitamin A, sodium arsenate and clofibrate) have been used to induce these disorders. The administration of a single dose of each of these three agents during the primitive streak stage of embryonic development in the golden hamster resulted in a variety of axial skeletal (dysraphic) disorders, including the two mentioned above. Regardless of the teratogen used, the basichondrocranium in both CSOEN and in CSA-EX is shorter than normal and slightly lordotic to the vertebral axis. Theshortness of the basichondrocranium in these two disorders is caused mainly by the shortness of the basioccipital. Both the shortness of the base of the skull and its lordotic or elevated position in relation to the vertebral axis are more pronounced in CSA-EX than in CSO-EN. The intracranial course of the notochord in these two axial disorders is considered to be within normal limits. However, the notochord itself is shorter than normal and depicts terminal folds which are considered to be the result of crowding. Both the shortness of the notochord and its terminal folding are also more pronounced in CSA-EXthan in CSO-EN. The sole difference encountered betwesn the abnormal basichondrocraniumsof these two disorders is in the severity of their common malformations (quantitative differences), but not in their type or quality. These findings give further support to the idea that these two principal developmental variations encountered are those pertaining to: (o) the overall intracranial course of the notochord; (b) the specific relationships of the notochord to the basioccipital and the basisphenoid; and (c) the notochordal relationship (or the lack of it) to the pharyngeal epithelium, and hence, its close association with the development of the bursa pharyngea in some mammals (e.g. man). The segmental nature of the notochordal enlargements of the basioccipital, found in the human and hamster embryos studied here, as well as their relation to the somitic origin of thisbone, have been analyzed and discussed. The present study has also emphasized the need to understand the developmental variations of the notochordal-basichondrocranium relationships among mammalian embryos for the study and interpretation of both clinically, as well as experimentally, induced malformations of the base of the skull. axial skeletal disorders are not different types of malformations, but different degrees of the same basic abnormality. The CNS involvement (encephalocoele or exencephaly) is also considered to be secondary to the paraxial mesodermal insufficiency. It is believed, and supported by the present findings, that the normal development of the paraxial mesoderm is needed for the normal process of formation and subsequent elevation and closure of the neural folds . A primary paraxial insufficiency could result in the partial (encephalocoele) or the complete (exencephaly) failure of closure of the neural folds which characterizes this type of axial skeletal (dysraphic) disorder. In addition, the normal notochordal-basichondrocranium relationships have been investigated in a group of mammalian embryos including man, hamster, mouse, and several others gathered from the literature. The significant developmental variations of the intracranial course of the notochord, and of its relationships to the components of the basichondrocranium, found among different mammals have been emphasized and illustrated. The principal developmental variations encountered are those pertaining to: ( a ) the overall intracranial course of the notochord; ( b ) the specific relationships of the notochord to thebasioccipital and the basisphenoid; and ( c ) the notochordal relationship (or the lack ofit) to the pharyngeal epithelium, and hence, its close association with the development of the bursa pharyngea in some mammals (e.g. man). The segmental nature of the notochordal enlargements of the basioccipital, found in the human and hamster embryos studied here, as well as their relation to the somitic origin of this bone, have been analyzed anddiscussed. The present study has also emphasized the need to understand the developmental variations of thenotochordal-basichondrocranium relationships among mammalian embryos for the study and interpretation of both clinically, as well as experimentally, induced malformations of the base of the skull.