Early prenatal development of the human precommissural septum

The development of the septum was studied in human embryos and fetuses ranging from 8 to 24.5 weeks of menstrual age (22.2 to 216 mm crown-rump length). Neuroblasts migrating from the ventricular layer of the ventromedial hemispheric wall form a narrow intermediate layer that constitutes the primordial septum (8 weeks). Only a primordial nucleus of the diagonal band is identifiable within the gradually enlarging primordial septum at early stages. By 10 weeks the primordial septum is subdivided into medial and lateral zones. At 11.5 weeks well-defined medial nuclei and the nucleus of the diagonal band are evident within the medial zone. Differentiation within the lateral zone occurs by 12.5 weeks with the appearance of nucleus lateralis pars interna. Nucleus dorsalis is developing in the lateral zone by 14.5 weeks and, by 15.5 weeks, well-defined nuclei are present throughout the lateral zone. Further neuronal maturation and conformational changes result in the nearly adult appearance of the septum in older fetuses. Although a definite mediolateral differentiation-gradient occurs, individual nuclei appear to differentiate along their own longitudinal gradient. Evidence presented suggests that the earliest fibers within the primordial septum are related to the tuberculum olfactorium and the medial forebrain bundle, that septohippocampal fibers appear at 10 weeks, hippocamposeptal fibers by 11.5 weeks, and that, later, stria terminalis fibers develop. The suggested developmental relationships of the septum with the hypothalamus (and brainstem), tuberculum, hippocampus, and amygdala emphasizes its role as an internode in the limbic system.