We have used time-lapse imaging of acute cortical slices to study the migration of neurons from their sites of origin to their positions in the developing neocortex. We found that two distinct modes of cell movement, somal translocation and glia-guided locomotion, are responsible for the radial migration of neurons generated in the cortical ventricular zone. The former is the prevalent form of radial movement of the early-born cortical neurons, while the latter is adopted by those generated later in corticogenesis. Interneurons, found to originate in the ganglionic eminence, follow tangential migratory paths to reach the developing cortex. Upon reaching the cortex, these cells seek the ventricular zone using a mode of movement that we have termed 'ventricle-directed migration', before they migrate to their positions in the cortical plate. In addition to these forms of movement, we report here a unique morphological and migratory behavior for a population of cortical neurons. These cells are multipolar in form, and are highly motile in the formation and retraction of their processes. Based on these morphological features, we refer to this type of cells as 'branching cells' and attribute the phenotype to a subset of cortical interneurons.

The decision of ectodermal cells to adopt the sensory organ precursor fate in Drosophila is controlled by two classes of basic-helix-loop-helix transcription factors: the proneural Ac and Sc activators promote neural fate, whereas the E(spl) repressors suppress it. We show here that E(spl) proteins m7 and mγ are potent inhibitors of neural fate, even in the presence of excess Sc activity and even when their DNA-binding basic domain has been inactivated. Furthermore, these E(spl) proteins can efficiently repress target genes that lack cognate DNA binding sites, as long as these genes are bound by Ac/Sc activators. This activity of E(spl)m7 and mγ correlates with their ability to interact with proneural activators, through which they are probably tethered on target enhancers. Analysis of reporter genes and sensory organ (bristle) patterns reveals that, in addition to this indirect recruitment of E(spl) onto enhancers via protein-protein interaction with bound Ac/Sc factors, direct DNA binding of target genes by E(spl) also takes place. Irrespective of whether E(spl) are recruited via direct DNA binding or interaction with proneural proteins, the co-repressor Groucho is always needed for target gene repression.

It is believed that postmitotic neurons migrate away from their sites of origin in the germinal zones to populate distant targets. Contrary to this notion, we found, using time-lapse imaging of brain slices, populations of neurons positioned at various levels of the developing neocortex that migrate towards the cortical ventricular zone. After a pause in this proliferative zone, they migrate radially in the direction of the pial surface to take up positions in the cortical plate. Immunohistochemical analysis together with tracer labeling in brain slices showed that cells showing ventricle-directed migration in the developing cortex are GABAergic interneurons originating in the ganglionic eminence in the ventral telencephalon. We speculate that combinations of chemoattractant and chemorepellent molecules are involved in this ventricle-directed migration and that interneurons may seek the cortical ventricular zone to receive layer information.