PURKINJE CELL PHENOTYPE RESTRICTS THE DISTRIBUTION OF UNIPOLAR BRUSH CELLS
PURKINJE CELL PHENOTYPE RESTRICTS THE DISTRIBUTION OF UNIPOLAR BRUSH CELLS
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DOI：
10.1016/j.neuroscience.2009.09.080
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发表时间：
2009-12-29
期刊：
影响因子：
3.3
通讯作者：
Hawkes, R.
中科院分区：
文献类型：
--
作者：
Chung, S. -H.;Sillitoe, R. V.;Hawkes, R.
小脑单极刷细胞（UBC）是颗粒层的谷氨酸能中间神经元。先前的研究已经确定了小鼠小脑皮质中的三个不同的 LIBC 子集：一个表达钙结合蛋白钙结合蛋白 (CR)，第二个表达代谢型谷氨酸受体 (mGluR)1 α 和磷脂酶 C(PLC)β 4，第三个表达 PLC beta 4 但不表达 mGluR1 α。我们研究了两种突变小鼠品系的 UBC 拓扑结构：早期 B 细胞因子 2 (Ebf2) null 和 scrambler。在 Ebf2 缺失小鼠中，浦肯野细胞形态因浦肯野细胞死亡和异位基因表达而被破坏。所有三类 UBC 的形貌也异常：通常与 zebrin II 条纹对齐的 CR+ UBC 变得均匀分布； mGluR1 α(+) UBC 的数量密度增加；许多 PLC beta 4(+) UBC 位于异位。 LIBC 异位不是 Ebf2 基因的细胞固有作用，对 Ebf2 启动子控制下的 β-半乳糖苷报告基因的组成型表达进行分析表明，在小脑发育的任何阶段，UBC 中都没有 Ebf2 表达。在扰码器 (Dab1(scm)) 中，大多数浦肯野细胞是异位的，但仍然具有正常的成体基因表达模式。在扰码器中，UBC 与特定的异位浦肯野细胞簇相关。最后，在正常小脑发育过程中也观察到与特定浦肯野细胞簇的类似关联。这些数据表明，UBC 在发育过程中通过涉及胚胎与不同浦肯野细胞亚型相互作用的非细胞自主机制而受到区域限制。 (C) 2009 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Cerebellar unipolar brush cells (UBCs) are glutamatergic interneurons of the granular layer. Previous studies have identified three distinct LIBC subsets in the mouse cerebellar cortex: one expressing the calcium-binding protein calretinin (CR), a second expressing both the metabotropic glutamate receptor (mGluR)1 alpha and phospholipase C(PLC)beta 4, and a third expressing PLC beta 4 but not mGluR1 alpha. We have investigated UBC topography in two strains of mutant mice: early B-cell factor 2 (Ebf2) null and scrambler. In Ebf2 null mice Purkinje cell topography is disrupted due to Purkinje cell death and ectopic gene expression. The topography of all three classes of UBCs is also abnormal: the CR+ UBCs, which are normally aligned with zebrin II stripes, become homogeneously distributed; the numerical density of mGluRl alpha(+) UBCs is increased; and many PLC beta 4(+) UBCs are located ectopically. The LIBC ectopia is not a cell-intrinsic action of the Ebf2 gene-analysis of the constitutive expression of a beta-galactoside reporter under the control of the Ebf2 promoter reveals no Ebf2 expression in UBCs at any stage of cerebellar development. In scrambler (Dab1(scm)), most Purkinje cells are ectopic but nevertheless have normal adult gene expression patterns. In scrambler, UBCs associate with specific ectopic Purkinje cell clusters. Finally, similar associations with specific Purkinje cell clusters are seen during normal cerebellar development. These data suggest that UBCs become regionally restricted during development through a non-cell-autonomous mechanism involving embryonic interactions with different Purkinje cell subtypes. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.