Timing of Cortical Interneuron Migration Is Influenced by the Cortical Hem

Abstract

Cerebral cortical γ-aminobutyric acid (GABA)ergic interneurons originate from the basal forebrain and migrate into the cortex in 2 phases. First, interneurons cross the boundary between the developing striatum and the cortex to migrate tangentially through the cortical primordium. Second, interneurons migrate radially to their correct neocortical layer position. A previous study demonstrated that mice in which the cortical hem was genetically ablated displayed a massive reduction of Cajal-Retzius (C-R) cells in the neocortical marginal zone (MZ), thereby losing C-R cell-generated reelin in the MZ. Surprisingly, pyramidal cell migration and subsequent layering were almost normal. In contrast, we find that the timing of migration of cortical GABAergic interneurons is abnormal in hem-ablated mice. Migrating interneurons both advance precociously along their tangential path and switch prematurely from tangential to radial migration to invade the cortical plate (CP). We propose that the cortical hem is responsible for establishing cues that control the timing of interneuron migration. In particular, we suggest that loss of a repellant signal from the medial neocortex, which is greatly decreased in size in hem-ablated mice, allows the early advance of interneurons and that reduction of another secreted molecule from C-R cells, the chemokine SDF-1/CXCL12, permits early radial migration into the CP.