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LDB1 对于背侧端脑和丘脑的早期发育是必需的。

LDB1 Is Required for the Early Development of the Dorsal Telencephalon and the Thalamus.

机构信息

Department of Life Sciences, Sophia College for Women, Mumbai 400026, India.

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.

出版信息

eNeuro. 2019 Mar 12;6(1). doi: 10.1523/ENEURO.0356-18.2019. eCollection 2019 Jan-Feb.

Abstract

LIM domain binding protein 1 (LDB1) is a protein cofactor that participates in several multiprotein complexes with transcription factors that regulate mouse forebrain development. Since null mutants display early embryonic lethality, we used a conditional knockout strategy to examine the role of LDB1 in early forebrain development using multiple Cre lines. Loss of from E8.75 using Foxg1Cre caused a disruption of midline boundary structures in the dorsal telencephalon. While this Cre line gave the expected pattern of recombination of the floxed locus, unexpectedly, standard Cre lines that act from embryonic day (E)10.5 (Emx1Cre) and E11.5 (NesCre) did not show efficient or complete recombination in the dorsal telencephalon by E12.5. Intriguingly, this effect was specific to the floxed allele, since three other lines including floxed Ai9 and mTmG reporters, and a floxed line, each displayed the expected spatial patterns of recombination. Furthermore, the incomplete recombination of the floxed locus using NesCre was limited to the dorsal telencephalon, while the ventral telencephalon and the diencephalon displayed the expected loss of . This permitted us to examine the requirement for LDB1 in the development of the thalamus in a context wherein the cortex continued to express . We report that the somatosensory VB nucleus is profoundly shrunken upon loss of LDB1. Our findings highlight the unusual nature of the locus in terms of recombination efficiency, and also report a novel role for LDB1 during the development of the thalamus.

摘要

LIM 结构域结合蛋白 1(LDB1)是一种蛋白辅因子,它与转录因子一起参与几个多蛋白复合物,调节小鼠前脑的发育。由于 LDB1 缺失突变体表现出早期胚胎致死性,我们使用条件性敲除策略,利用多个 Cre 线研究 LDB1 在早期前脑发育中的作用。从 E8.75 开始利用 Foxg1Cre 敲除 LDB1 导致背侧端脑中线边界结构的破坏。虽然这种 Cre 线产生了预期的 floxed 基因座的重组模式,但出乎意料的是,作用于胚胎日(E)10.5(Emx1Cre)和 E11.5(NesCre)的标准 Cre 线在 E12.5 时并未在背侧端脑中显示出有效的或完全的重组。有趣的是,这种效应是 floxed 等位基因特有的,因为包括 floxed Ai9 和 mTmG 报告基因在内的另外 3 条线以及一条 floxed 等位基因线,每条线都显示出预期的重组空间模式。此外,NesCre 对 floxed 基因座的不完全重组仅限于背侧端脑,而腹侧端脑和间脑则显示出预期的 LDB1 缺失。这使我们能够在皮层继续表达 LDB1 的情况下,研究 LDB1 在丘脑发育中的需求。我们报告说,在 LDB1 缺失后,感觉 VB 核明显缩小。我们的研究结果突出了 基因座在重组效率方面的独特性质,也报告了 LDB1 在丘脑发育中的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e0/6416242/3b2a613a9656/enu0011928740001.jpg

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