The origin of large neurons of the substantia nigra, ventral tegmental area of Tsai and interpeduncular nucleus was determined in three-weekold rats receiving a single injection of thymidine-H" during gestation. These neurons underwent final mitotic division on embryonic days 11 through 15 with maximal production on days 1 4 and 15. Glia and the smallest type of granular neurons were produced from day 11 through 22. Cells in the ventral angle of the neuroepithelium were not labeled one hour after injection of thymidine-H3 in any of the series.Study of animals receiving a single injection of thymidine-H3 during gestation and killed at serial intervals thereafter showed that neurons forming the substantia nigra migrated from the middle third of the basal neuroepithelium and moved between existing cells in radial patterns. Production of neurons specifically for each division of the substantia nigra was not observed either in crosssection or rostrocaudally, nor was the destination of neurons related to their time of origin. The ventral tegmental area of Tsai and interpeduncular nucleus formed from neurons originating in the medial third of the basal plate and migrating almost to the ventral surface of the mesencephalon. The neurons then divided into two streams to create a pattern of an inverted fountain comparable to the distribution of neurons containing catecholamines. Some of these neurons may have contributed to the substantia nigra. The primordia in all three nuclear areas were first seen on embryonic day 18.
To examine the formation and differentiation of the external granular layer, chick embryos ranging in age from two to 20 days were treated with tritiated thymidine and sacrificed after various time intervals. By studying the migration of the labeled cells at different stages of development, the following observations were made: (1) cells originating from the neuro-epithelial layer along the ventricular surface of the cerebellar plate migrate through previously formed cell layers of neuroblasts to the surface; (2) the development of the lateral portion of the cerebellar plate is approximately 24 hours more advanced than that of the medial region, thus explaining the appearance of the external granular layer first laterally and then medially; (3) at no time during development can a proliferation center be found in the ventrolateral angle of the fourth ventricle. Based on these results, it is concluded that the cells of the external granular layer originate from the neuroepithelium bordering the ventricular surface of the cerebellar plate and migrate from this position straight to the surface. No evidence for a surface migration from the ventrolateral angle in a dorsomedial direction can be found.Shortly after the formation of the external granular layer at day six, its cells begin to proliferate. During this period, which lasts until day 15, relatively few cells leave the external granular layer to migrate inwards. After this day a massive inward migration occurs, and the cells of the external granular layer differentiate into the granular cells and perhaps the glia cells. In the internal granular layer they intermingle with the Purkinje cells and Golgi I1 neurons, which originate in the neuroepithelial layer between days three and six of development. Shortly after hatching, when the external granular layer has fulfilled its function in cell production, it disappears.
Interkinetic nuclear migrations studied by radioautography in the medullar neuroepithelium of the 14-day rat embryo are similar to those in other areas of the neuraxis in other species. The cell cycle lasts approximately 12 hours. Olivary neurons are produced along the length of the alar plate on embryonic days 14 and 15, mostly on day 14. Between 36 and 48 hours after injection of thymidine-H3, labeled cells migrate into the mantle layer and are more concentrated in the alar lamina than in the basal lamina, The olivary primordium appears in the ventromedial medulla on day 17 and is almost mature by day 21. Labeled neurons in the alar lamina migrate to the primordium in two bands, the marginal and the submarginal migration strands. From these strands, labeled cells move into the ventrolateral and ventromedial portions of the olivary complex. Newly arrived neurons push the existing cells dorsally. By embryonic day 21, as proliferation of cells in the neuroepithelium ceases, the migration strands disappear, and the olive is fully formed.
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