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PKN1在视网膜细胞类型形成中的作用。

Role of PKN1 in Retinal Cell Type Formation.

作者信息

Brunner Magdalena, Lang Luisa, Künkel Louisa, Weber Dido, Safari Motahareh Solina, Baier-Bitterlich Gabriele, Zur Nedden Stephanie

机构信息

Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.

出版信息

Int J Mol Sci. 2024 Feb 29;25(5):2848. doi: 10.3390/ijms25052848.

Abstract

We recently identified PKN1 as a developmentally active gatekeeper of the transcription factor neuronal differentiation-2 (NeuroD2) in several brain areas. Since NeuroD2 plays an important role in amacrine cell (AC) and retinal ganglion cell (RGC) type formation, we aimed to study the expression of NeuroD2 in the postnatal retina of WT and animals, with a particular focus on these two cell types. We show that PKN1 is broadly expressed in the retina and that the gross retinal structure is not different between both genotypes. Postnatal retinal NeuroD2 levels were elevated upon knockout, with retinae showing more NeuroD2 cells in the lower portion of the inner nuclear layer. Accordingly, immunohistochemical analysis revealed an increased amount of AC in postnatal and adult retinae. There were no differences in horizontal cell, bipolar cell, glial cell and RGC numbers, nor defective axon guidance to the optic chiasm or tract upon knockout. Interestingly, we did, however, see a specific reduction in SMI-32 α-RGC in retinae. These results suggest that PKN1 is important for retinal cell type formation and validate PKN1 for future studies focusing on AC and α-RGC specification and development.

摘要

我们最近确定PKN1是几种脑区中转录因子神经分化-2(NeuroD2)在发育过程中的活性调控因子。由于NeuroD2在无长突细胞(AC)和视网膜神经节细胞(RGC)类型形成中起重要作用,我们旨在研究野生型和[缺失PKN1的]动物出生后视网膜中NeuroD2的表达情况,特别关注这两种细胞类型。我们发现PKN1在视网膜中广泛表达,且两种基因型动物的视网膜总体结构并无差异。敲除[PKN1]后出生后视网膜NeuroD2水平升高,[缺失PKN1的]视网膜在内核层下部显示出更多的NeuroD2阳性细胞。相应地,免疫组织化学分析显示出生后和成年[缺失PKN1的]视网膜中AC数量增加。水平细胞、双极细胞、神经胶质细胞和RGC的数量没有差异,敲除[PKN1]后轴突向视交叉或视束的引导也无缺陷。有趣的是,然而,我们确实在[缺失PKN1的]视网膜中看到SMI-32 α-RGC有特定减少。这些结果表明PKN1对视网膜细胞类型形成很重要,并为未来聚焦于AC和α-RGC的特化与发育的研究验证了PKN1。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edc/10931565/7a023a8059fe/ijms-25-02848-g004.jpg

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