Cxcr4 和 Ackr3 调节尾状核神经节源性中间神经元分配到皮质浅层。

Cxcr4 and Ackr3 regulate allocation of caudal ganglionic eminence-derived interneurons to superficial cortical layers.

机构信息

Institute of Pharmacology and Toxicology, University Hospital Jena, Jena, Germany.

出版信息

Cell Rep. 2022 Aug 2;40(5):111157. doi: 10.1016/j.celrep.2022.111157.

DOI:10.1016/j.celrep.2022.111157

Abstract

The function of the cerebral cortex depends on various types of interneurons (cortical interneurons [cINs]) and their appropriate allocation to the cortical layers. Caudal ganglionic eminence-derived cINs (cGE-cINs) are enriched in superficial layers. Developmental mechanisms directing cGE-cINs toward superficial layers remain poorly understood. We examine how developmental and final positioning of cGE-cINs are influenced by the Cxcl12, Cxcr4, Ackr3 module, the chief attractant system guiding medial ganglionic eminence-derived cINs (mGE-cINs). We find that Cxcl12 attracts cGE-cINs through Cxcr4 and supports their layer-specific positioning in the developing cortex. This requires the prevention of excessive Cxcr4 stimulation by Ackr3-mediated Cxcl12 sequestration. Postnatally, Ackr3 confines Cxcl12 action to the marginal zone. Unlike mGE-cINs, cGE-cINs continue to express Cxcr4 at early postnatal stages, which permits cGE-cINs to become positioned in the forming layer 1. Thus, chemoattraction by Cxcl12 guides cGE-cINs and holds them in superficial cortical layers.

摘要

大脑皮层的功能取决于各种类型的中间神经元（皮质中间神经元[cIN]）及其在皮质层中的适当分配。尾状核隆起源性 cIN（cGE-cIN）富含于浅层。指导 cGE-cIN 向浅层迁移的发育机制仍知之甚少。我们研究了 Cxcl12、Cxcr4、Ackr3 模块如何影响 cGE-cIN 的发育和最终定位，该模块是引导内侧神经节隆起源性 cIN（mGE-cIN）的主要吸引系统。我们发现 Cxcl12 通过 Cxcr4 吸引 cGE-cIN，并支持它们在发育中的皮质中的特定层定位。这需要 Ackr3 介导的 Cxcl12 隔离来防止 Cxcr4 过度刺激。出生后，Ackr3 将 Cxcl12 作用局限于边缘区。与 mGE-cIN 不同，cGE-cIN 在出生后早期阶段继续表达 Cxcr4，这使得 cGE-cIN 能够定位于正在形成的第 1 层。因此，Cxcl12 的趋化吸引指导 cGE-cIN 并将其保持在浅层皮质中。