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

Abstract

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.

Regional Distribution of Cortical Interneurons and Development of Inhibitory Tone Are Regulated by Cxcl12/Cxcr4 Signaling

“…Furthermore, the ventral-to-dorsal gradients within the cortical SVZ and cortical plate, may regulate their tangential dispersion. In contrast, as has been reported in detail by others (Stumm et al, 2003(Stumm et al, , 2007Tissir et al, 2004;Daniel et al, 2005), the Cxcl12 receptor Cxcr4 is weakly expressed in the migrating interneurons entering the cortex at both E13.5 and E16.5 [supplemental The distribution pattern of Cxcl12 in the meninges and SVZ suggests that it may play a role in organizing interneurons into streams, whereas the tapering pattern of Cxcl12 in the SVZ may facilitate the lateralto-medial dispersion of interneuron. Moreover, the spatial gradient (high in meninges to low in SVZ) and the temporal gradient (low at E13.5 to high at E16.5) of Cxcl12 suggest it may play a critical role in the MZ accumulation of interneurons in that particular time window.…”

“…1, available at www.jneurosci.org as supplemental material). Because Cxcl12 continues to be expressed in the meninges during that time window (Stumm et al, 2003(Stumm et al, , 2007, it raises the issue of how the GFPϩ cells adjust their responsiveness to Cxcl12 during this period; either the GFPϩ cells change their responsiveness (losing their attractive response or becoming repulsed by Cxcl12), or the cues that drive the radial migration are dominant over Cxcl12. To address this, we examined Cxcl12 responsiveness during this time period by placing Cxcl12-soaked beads into the cortical plate of P0 cultured slices.…”

Nutritional factors and aging in demyelinating diseases

“…Certain chemokines, such as CXCL12 and CXCL1, are induced during CNS development and coordinate the proliferation, migration, and differentiation of neural precursor cells (NPCs) (Stumm et al 2007;Tsai et al 2002), which suggests they might also participate in CNS regenerative processes. In this way, Patel et al (2010) demonstrated that CXCR4 (the receptor of CXCL12) activation is important for the remyelination of the CPZ-demyelinated mouse by induction of OPC differentiation.…”

Chemokine Signaling Controls Intracortical Migration and Final Distribution of GABAergic Interneurons

“…Recently, it has been reported that CXCL12, a member of the CXC subfamily of chemokines [also known as SDF-1 (stromal cell-derived factor-1)], is expressed in the meninges and in the SVZ of the developing cortex in a pattern that is consistent with a role for this molecule in the intracortical guidance of GABAergic interneurons (Stumm et al, 2003;Tiveron et al, 2006;Stumm et al, 2007). However, to what extent this signaling system is directly required for the migration of interneurons within the cortex and how this process may influence their final distribution in the cortex remains to be elucidated.…”