Patterns of SDF‐1α and SDF‐1γ mRNAs, migration pathways, and phenotypes of CXCR4‐expressing neurons in the developing rat telencephalon

Cortical GABAergic neurons originate in the ventral telencephalon, invade the cortex via tangential migration, and integrate into the cortical plate by surface-directed and ventricle-directed migration. In mice lacking CXCR4 or SDF-1, GABAergic neurons fail to complete their migration. It is presently unknown which parts of the migration of CXCR4-expressing GABAergic neurons are driven by SDF-1. Here we compared patterns of SDF-1 isoforms and CXCR4 in the developing rat telencephalon. In the ventral telencephalon, radial glia, striatal, and migratory GABAergic neurons expressed CXCR4. Tangentially migrating CXCR4-expressing neurons populated the marginal zone and started to invade the lateral intermediate zone at embryonic day (E)14. Until E17 the spread of CXCR4-expressing neurons in the dorsomedial direction was accompanied by progressive upregulation of SDF-1alpha in the dorsomedial intermediate/subventricular zone. In the meninges, SDF-1alpha and SDF-1gamma were expressed persistently. During invasion of the cortical plate the orientation of CXCR4-immunoreactive neurons changed gradually from tangential (E17/E18) to radial (postnatal day [P] 0), which was paralleled by downregulation of SDF-1alpha in the intermediate/subventricular zone. At E17, CXCR4-immunoreactive cells were colabeled with markers for ventral forebrain-derived neurons (Dlx) but not markers for glutamatergic (Tbr) or subplate (calretinin) neurons. Postnatally, calretinin- and somatostatin-expressing but not parvalbumin-expressing GABAergic neurons or pyramidal cells contained CXCR4. Pyramidal cells and few large blood vessels expressed SDF-1alpha, while microvessels contained SDF-1gamma transcripts. In summary, SDF-1alpha is expressed along cortical but not subcortical migration routes of GABAergic neurons. We propose that regulated expression of SDF-1 in the intermediate/subventricular zone influences lateromedial tangential migration of CXCR4-expressing GABAergic neurons.