Stumm Ralf, Kolodziej Angela, Schulz Stefan, Kohtz Jhumku D, Höllt Volker
Institute of Pharmacology and Toxicology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany.
J Comp Neurol. 2007 May 20;502(3):382-99. doi: 10.1002/cne.21336.
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.
皮质GABA能神经元起源于腹侧端脑，通过切向迁移侵入皮质，并通过表面导向和脑室导向迁移整合到皮质板中。在缺乏CXCR4或SDF-1的小鼠中，GABA能神经元无法完成其迁移。目前尚不清楚表达CXCR4的GABA能神经元迁移的哪些部分是由SDF-1驱动的。在这里，我们比较了发育中的大鼠端脑中SDF-1亚型和CXCR4的模式。在腹侧端脑中，放射状胶质细胞、纹状体和迁移的GABA能神经元表达CXCR4。在胚胎第（E）14天，切向迁移的表达CXCR4的神经元聚集在边缘区并开始侵入外侧中间区。直到E17，表达CXCR4的神经元在背内侧方向的扩散伴随着背内侧中间/室下区SDF-1α的逐渐上调。在脑膜中，SDF-1α和SDF-1γ持续表达。在侵入皮质板期间，CXCR4免疫反应性神经元的方向逐渐从切向（E17/E18）变为放射状（出生后第[P]0天），这与中间/室下区SDF-1α的下调平行。在E17时，CXCR4免疫反应性细胞与腹侧前脑衍生神经元（Dlx）的标记物共标记，但不与谷氨酸能（Tbr）或皮质下板（钙视网膜蛋白）神经元的标记物共标记。出生后，表达钙视网膜蛋白和生长抑素但不表达小白蛋白的GABA能神经元或锥体细胞含有CXCR4。锥体细胞和少数大血管表达SDF-1α，而微血管含有SDF-1γ转录本。总之，SDF-1α沿GABA能神经元的皮质迁移途径而非皮质下迁移途径表达。我们提出，中间/室下区SDF-1的调节表达影响表达CXCR4的GABA能神经元的内外侧切向迁移。
