Figure 4.

Development of projection neurons in the mouse cerebral cortex. The neural stem/progenitor cells of the cerebral cortex or radial glial cells (RGs) are highly polarized cells that are attached to one another in the ventricular zone (VZ) by apically located adherens junctions (AJ) ❶. Their nuclei migrate during cell cycle progression from a basal position during S phase to an apical position during mitosis (M), and the nuclei of the daughter cells migrate back to enter S phase on the basal side of the VZ, in a process called interkinetic nuclear migration (INM) ❷. During the peak of neurogenesis, most radial glial cells divide asymmetrically with a vertical cleavage plane ❸. In these divisions, one daughter remains a RG and continues to divide at the ventricular surface, whereas the other detaches from the ventricular surface, move radially away to the subventricular zone (SVZ)/lower intermediate zone (IZ) and acquires a multipolar shape ❹. Then, nascent neurons become bipolar, extending a leading process toward the pial surface and a trailing process in the opposite direction ❺. Upon multi to bipolar transition, newborn neurons establish contacts with RG fibers and subsequently use them as a scaffold to migrate to the upper part of the cortical plate (CP) using a mode of migration called locomotion ❻. During this phase the trailing process becomes the axon and extends to its final destination. Once cortical neurons reach the upper part of the CP and right after their leading process makes contact with the marginal zone (MZ), they detach from the RG fibers and execute a terminal somal translocation ❼. The leading process then gives rise to the apical dendrite, which initiates local branching in the MZ ❽. Basal dendrites subsequently appear as well as oblique side branches emerging from the apical shaft ❾. At this stage, the cell body of early-born neurons translocate ventrally as neurons born at later stages bypass their predecessors. The final step in cortical projection development is the apparition and maturation of spines. For example, in layer V pyramidal neurons, spines are morphologically mature at P21 on apical dendrites ❿.