The guidance of growing axons

Sulik I, K.K., and Lauder 2, J.M. Departments of Anatomyl, 2 and Ophthalmology I, University of North Carolina, Chapel Hill, N.C. 27514 Deficiencies of the antero-medial aspect of the embryonic dis~result from acute maternal alcohol administration to C57BI/6J mice by either the i.p. or gastric intubation route on gestational day 7. Subsequent defects of the brain and face are consistent with those observed in severe human fetal alcohol syndrome (FAS). Light and scanning electron microscopic (SEM) analyses of brain morphogenesis i l lustrate a wide s p e ~ trum of defects which primarily involve the ventro-medial forebrain. At the mild end of the spectrum minor deficiencies are observed in the developing septal nuclei, whereas in the most severely affected animals many defects in anterior brain development are found which are consistent with those commonly recognized as belonging to the holoprosencephaly series. Among these defects are fusion of paired medial structures, (e.g., the septal nuclei), enlarged lateral ventricles, narrowing of the third ventricle, thinning of the cerebral cortex, and absence of the corpus callosum. Acute alcohol exposure may interfere with gastrulat ion and secondari ly affect neural plate induction via a deficiency in prechordal mesoderm. The insult to the neural plate may be direct, or teratogenesis may involve indirect mechanisms. These studies demonstrate that a "crit ical period" for alcohol neuro-teratogenesis exists which corresponds to the third week of human gestation. Supported by DISCUS Grant 1722-017 and NIH grant NS 15706.