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

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 E15 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 at 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 at 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.