Commentary: Coordinating Thalamocortical Connections and Interneuron Migration in the Mammalian Cortex: Role of the Intermediates

During embryogenesis, thalamocortical axons (TCAs) organize themselves in defined bundles that follow a unique pathway crossing several anatomical boundaries, which makes them easy to track during different stages of neocortical development. These features render TCAs notoriety as a model to study the extrinsic cues that regulate axon guidance and elongation in vertebrate systems. Amid neocortical development, corticothalamic axons (CTAs), project to the subpallium to target the thalamic and subcortical areas, whereas the ascending TCAs project through the ventral telencephalon toward the pallium and spread to reach diverse regions of the neocortex (Garel and Lopez-Bendito, 2014). TCAs advance through the subpallial region, moving slowly at the pallial-subpallial boundary (PSPB) and meet the corticofugal axons approximately around E14. At around E16, TCAs transit via the intermediate zone (IZ) and ascend to the cortical plate in order to make appropriate networks by creating synaptic contacts to the cortical neurons (Maroof and Anderson, 2006). TCAs trajectory through the subpallium is influenced by locally secreted Netrin-1 (Braisted et al., 2000), followed by progression into the pallium as a response to the timely release of neuregulin, which concomitantly promotes the tangential migration of interneurons (Lopez-Bendito et al., 2006). Interneurons are generated from several progenitor pools at defined proliferative foci in the ganglionic eminences of the subpallium (Flames et al., 2007). Newly formed INs become bipolar and initiate migration toward the cortex following a characteristic tangential migration. The crosstalk between local repulsion and distal chemo-attraction delineates two clear migratory corridors that enable INs to populate the neocortex, one flowing through the marginal zone (MZ) and the second through the SVZ/IZ (Peyre et al., 2015). Chemokines containing the CXC motif (conserved cysteine residues separated by an amino acid) play a central role in axonal progression by activating their receptors at axon growth cones, thus triggering a towing mechanism that promotes their elongation and ensures target meeting (Gilmour et al., 2004; Lieberam et al., 2005). In the mammalian cortex, stromal cell-derived