| The neocortex contains excitatory neurons and inhibitory interneurons. Previous studies revealed that clones of neocortical excitatory neurons originating from the same progenitor cell are spatially organized and contribute to the formation of functional microcircuits. In contrast, little is known about the production and organization of neocortical inhibitory interneurons. Here, we show that radial glial cells in the ventricular zone of the medial ganglionic eminence (MGE) undergo asymmetric cell division at the ventricular zone surface to self-renew and to simultaneously produce differentiating interneurons or intermediate progenitor cells that migrate away from the ventricular zone. Intermediate progenitor cells further divide symmetrically in the subventricular zone to produce differentiating interneuron pairs. Interestingly, the progeny of the same radial glial progenitor cell closely associate with the radial process of the mother radial glial cell, organizing into a radial cluster in the MGE. As development proceeds, the early-born daughter cells gradually acquire the characteristic morphology and biophysical properties of migrating interneurons, detach from the mother radial glial cell and embark on a tangential migration route towards the neocortex. These results reveal that, similar to excitatory neurons, inhibitory interneurons in the neocortex are produced as spatially organized clonal units. Furthermore, contrary to the current view of tangential migration of neocortical interneurons, clonally related interneurons do not randomly disperse, but form isolated clusters in the neocortex. Moreover, individual clonal clusters consisting of the same or distinct subgroups of interneurons exhibit clear vertical or horizontal organization. These results strongly suggest that the lineage relationship plays a pivotal role in the organization of inhibitory interneurons in the neocortex. |
