The development of the cerebral cortex in the embryonic mouse: An electron microscopic serial section analysis

Abstract

The techniques of reconstructions of cells from serial thin sections and autoradiography after tritiated thymidine injections have been employed to study the early histogenesis of the cerebral cortex in the embryonic day-15 (E15) mouse. The autoradiographic studies show that cells below the E l 5 cortical plate in the intermediate layer are destined to migrate through the preexisting cortical plate cells to take up a more superficial position. Having this information, it has been possible, through reconstructions of large numbers of cells (more than 150) throughout the thickness of the cerebral vesicle, to identify some of the important morphogenetic events of cortical histogenesis. The following scheme is proposed. The first step in neuronal differentiation involves the detachment of the ventricularly directed process of the ventricular cell from the junctional region next to the ventricle. In thin sections, these junctions have the appearance of zonulae adherentes, but freeze cleavage experiments performed in this study show that, in addition, some of them resemble small gap junctions while others appear to be remnants of tight junctions or possibly linear gap junctions. Detachment of the ventricular process accompanies the migration of the nucleus and perikaryon through the ventricular layer. Within the intermediate layer the migrating cells become rounded and sprout numerous processes. Some cells may undergo a mitotic division a t this stage. Eventually the differentiating cells sprout a longer lateral process which is oriented tangentially to the pial surface. This process originates from the anterior surface of the soma and a t its tip has the characteristics of an axonal growth cone. The cells migrate externally and radially with simultaneous elongation of the primitive axon. In the subcortical plate region of the intermediate layer all cells contain an anteriorly directed axon. Subsequently, the cells sprout an apical process which extends into the cortical plate, and the nucleus and perikaryon apparently migrate radially within this process. The result is that the primitive axon first descends into the intermediate layer proper before turning to run tangentially. Dendritic growth and further differentiation begins once the cells reach their definitive position in the cortical plate.One interesting finding is the presence of eight cells in the cortical plate without long anteriorly directed axons. Yet, autoradiographic data show that subcortical plate cells are the immediate precursors of cortical plate cells, and all 28/28 reconstructed subcortical plate cells have long anteriorly directed axons. Thus, it is possible that the long axon of some cells may be lost as the cells continue to differentiate in the cortical plate. In fact, one cell has been found which appears to be in the process of losing its anteriorly directed axon.A number of molecular layer cells have also been reconstructed. These cells have several processes oriented tangentially to the pial surface. The identity of these processe...

Mitotic spindle rotation and mode of cell division in the developing telencephalon

“…This system maintains the architectonic nature of the neocortical wall and is conducive to the study of proliferative kinetics during neocortical growth. The time-lapse procedure elucidated the remarkable and dynamic nature of the embryonic VZ, with all VZ progenitors exhibiting interkinetic movements (3,(29)(30)(31)(32)(33)(34)(35) and cell division simultaneously in each field (see Movies 1 and 2).…”

Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon

“…The band of TuJlpositive cells along the ventricular zone-subventricular zone border may restrain the to-and-fro movement of the nuclei, characteristic of the proliferating cells of the ventricular zone (see Takahashi et al, 1993). Another role the TuJ 1 -positive cells may serve, at the border between the ventricular and subventricular zones, is to exclude axons from the ventricular zone (Shoukimas and Hinds, 1978;Edwards et al, 1989). When labeled with DiI, corticothalamic, corticosubcortical, and corticocortical axons never penetrate the ventricular zone of the cerebral cortex and striatum (Menezes and Luskin, unpublished observations).…”

“…Nevertheless, the early steps of this differentiation process have remained elusive. Early autoradiographic and electron microscopic studies (Fujita, 1963;Meller et al, 1966;Hinds and Ruffett, 197 1;Meller and Tetzlaff, 1975;Shoukimas and Hinds, 1978) characterized the ventricular zone as a homogeneous population of asynchronously proliferating cells. To the contrary, in recent years it has been shown that by the onset of cortical neurogenesis distinct glial and neuronal progenitor cells are present within the ventricular zone (Schmechel and Rakic, 1979;Levitt et al, 198 1, 1983;Luskin et al, 1988Luskin et al, , 1993, and that the first appearance of radial glia is an even earlier event (Gressens et al, 1992).…”

Initiating and Growing an Axon

“…In other neuronal subpopulations undergoing long-range migration, neuronal morphogenesis undergoes extensive stereotypical changes, leading to polarized outgrowth of their axon and dendrites. This is the case for cerebellar granule neurons (CGN) as well as cortical and hippocampal pyramidal neurons (PN), two of the best-studied models of neuronal polarization (Rakic 1971;Rakic 1972;Shoukimas and Hinds 1978;Gao and Hatten 1993;Komuro et al 2001;Hatanaka and Murakami 2002;Noctor et al 2004). Both CGN and PN acquire their axon -dendrite polarity from the polarized emergence during migration of their trailing and leading processes, respectively (Fig.…”