Cycle times of the neural epithelial cells of various types of neuron in the rat. An autoradiographic study

Abstract

Cell kinetic studies of the proliferation of the neural epithelium during the embryonic development of the rat brain are described.Pregnant rats received a single injection of "-thymidine PH-TdR) between the tenth and twenty-first day of pregnancy. Autoradiographs of the brains of the 25-day-old offspring were prepared. For a number of different cell types (table 1 , 11) the percentage of labeled neurons as a function of time of prenatal :'H-TdR injection was determined.The end of the proliferating period of the neural epithelial cells of certain cell types can be derived from these percentages of labeled cells (table 1 , V). Furthermore, i t can be demonstrated that the percentage of labeled neurons is equal to the labeling index of the neural epithelial cells of these cell types at the time of prenatal "H-TdR injection.Based on the labeling index of the neural epithelial cells and their S phase, cycle times can be calculated. This way it is possible for the first time to determine the cycle times of those neural epithelial cells that later on differentiate into a certain type of neuron (table 1, IV).The calculated cycle times show that up to the sixteenth prenatal day the neural epithelial cells behave like a homogeneous cell population which proliferates with an approximately constant cycle time of about half a day. The cycle time seems to increase with increasing fetal age.From the total number of a certain type of neuron the number of mitotic divisions or cycle times respectively can be derived which is necessary to produce the number of neural epithelial cells providing these neurons. With regard to the mean cycle time of the neural epithelial cells i t can be concluded that the beginning of proliferation of the neural epithelial cells coincides with the formation of the neural plate on the ninth day of embryonic development or starts even shortly before this time.Prenatal labeling with :3H-thymidine ("H-TdR) of the proliferating neural epithelial cells of the embryonic brain and the observation of labeled neurons in the young or adult animal has proved a useful tool in studying the development of the brain. Labeling of neurons can only be achieved if :jH-TdR is applied prenatally, prior to differentiation of the neural epithelial cells into neuroblasts (cells produced by the last division of neural epithelial cells that do not divide any more but differentiate into the corresponding neurons) and neurons. With this method the prenatal "time of origin" or "date of birth" of many types of neurons in the chick, the mouse and the rat has been studied.

Glutamate Promotes Proliferation of Striatal Neuronal Progenitors by an NMDA Receptor-Mediated Mechanism

“…These results are in agreement with previous reports suggesting that GABAergic medium spiny neurons and their precursors make up the majority of cells in these early cultures, with a minority of interneurons and glia (Ivkovic et al, 1997;Ventimiglia and Lindsay, 1998;Petersen et al, 2000). The results are also consistent with evidence that forebrain gliogenesis (with the exception of radial glia) occurs in the late prenatal and early postnatal periods (Schultze et al, 1974).…”

Cell-Cycle Kinetics of Neocortical Precursors Are Influenced by Embryonic Thalamic Axons

“…The influence of the thalamus-derived factor exclusively on the duration of the G 1 phase of the cell cycle is in agreement with a number of studies showing that, in most eukaryotic cell types, cell-cycle duration is regulated mainly via G 1 (Pardee, 1989) and that Ts and G 2 /M-phase duration are highly conserved during neurogenesis (Kaufmann, 1968;Waechter and Jaensch, 1972;Schultze et al, 1974;Schmahl, 1983;Reznikov and van der Kooy, 1995;Miyama et al, 1997).…”

“…The LI indicates the proportions of precursors in S phase at the time of the BrdUrd pulse and therefore reflects the relative duration of the S phase (Ts) with respect to the total duration of the cell cycle. Because Ts is largely invariant, variations of LI reflect changes in the duration of the cell cycle (Tc) (Waechter and Jaensch, 1972;Schultze et al, 1974;Schmahl, 1983;Reznikov and van der Kooy, 1995) (Fig. 5).…”

Regulation of Neuroblast Cell-Cycle Kinetics Plays a Crucial Role in the Generation of Unique Features of Neocortical Areas

“…Second is the duration of the cell cycle (Tc). S-phase is relatively invariant during cortical neurogenesis, and variations in the Tc are mostly attributable to G1 modification (Kaufmann, 1968;Waechter and Jaensch, 1972;Hoshino et al, 1973;Schultze et al, 1974;Korr, 1980;Schmahl, 1983;Miller and Kuhn, 1995;Reznikov and van der Kooy, 1995;Takahashi et al, 1995). Variations in the Tc lead to a variation of the percentage of precursors in S-phase so that after a pulse, short Tc values result in high labeling indices and long Tc values result in low labeling indices (Fujita, 1967;Waechter and Jaensch, 1972) (Fig.…”

“…To investigate the proliferative behavior of neuronal precursors, we injected an S-phase marker at different fetal stages and examined the intensity of autoradiographic labeling and the distribution of the cohorts of labeled neurons in the adult cortex (Schultze et al, 1974;Brückner et al, 1976). This makes it possible to describe the mitotic history of precisely defined neuronal populations (Sidman, 1970).…”