The development of the human brain, including the longitudinal zoning in the diencephalon at stage 15

Twenty-six embryos (6-11 mm) of stage 15 (approximately 33 days) were studied in detail and graphic reconstructions of three of them were prepared. Characteristic features of this stage include closed lens vesicles, presence of nasal pits, and retinal pigment. The neuromeric pattern is still visible. Each cerebral hemisphere is limited by the torus hemisphericus internally and by the di-telencephalic sulcus externally. The medial (diencephalic) eminence of the basal nuclei (previously misinterpreted by others as the lateral) had appeared in stage 14, and the lateral eminence, which is telencephalic, is now distinguishable. The amygdaloid body in stages 14 and 15 is derived from the medial eminence. The hippocampal thickening is identifiable in the dorsomedial part of the cerebral hemisphere. Medial and basal forebrain bundles are developing. The olfactory eminence is visible. Future olfactory bulb and tubercle possess an intermediate layer. The wall of the diencephalon presents five longitudinal zones: epithalamus, dorsal thalamus, ventral thalamus, subthalamus, and hypothalamus. The primordium of the epiphysis cerebri is beginning in the more advanced embryos. The sulcus limitans ends rostrally at the midbrain (M1) and is not continuous with the hypothalamic sulcus. Hence the alar/basal distinction does not arise in the forebrain. In the roof of the midbrain (M2) the mesencephalic evagination already noticed at stage 14 is characteristic. It is suggested that it may function as a temporary circumventricular organ. The precursors of some new tracts are identifiable: habenulo-interpeduncular, medial tectobulbar, and mamillotegmental fibres. Commissures include the supramamillary, that of the superior colliculi, and (in some embryos) the first fibres of the posterior commissure. Nuclei include the habenular, mamillary, and probably subthalamic. The cerebellum, the beginning of which was already noted at stages 13 and 14, consists of (1) a rostral part that arises from the alar plate of the isthmic segment and will form the superior medullary velum and part of the corpus cerebelli; and (2) a caudal part that develops from rhombomere 1. The involvement of the isthmic segment, first elucidated with stage 14, has not been observed in previous reports. All cranial nerves except the olfactory and optic are present in the more advanced embryos.