Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele.

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele.
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使用Cre重组酶敲入等位基因鉴定表达转录因子Brn 3c/Pou 4f 3的视网膜神经节细胞类型和脑核

DOI:
10.1002/cne.25065
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发表时间:
2021-06
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Badea TC
Badea TC
中科院分区:
其他
文献类型:
--
作者:
Parmhans N;Fuller AD;Nguyen E;Chuang K;Swygart D;Wienbar SR;Lin T;Kozmik Z;Dong L;Schwartz GW;Badea TC

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POU4F/Brn3转录因子家族的成员在视网膜神经节细胞类型(RGCs)的发育中起着既定的作用,RGC是从哺乳动物的眼睛到大脑的视觉信息的主要传递者。我们之前的工作利用表达碱性磷酸酶(AP)的条件性敲入报告等位基因的稀疏随机重组和交叉遗传学已经鉴定出三种类型的Brn3c阳性(Brn3c+)RGC。在这里,我们描述了一个由DRE到Cre序列重组产生的新的Brn3cCre小鼠等位基因,并利用它来探索Brn3c与Brn3a和Brn3b的表达重叠以及Brn3c+RGC类型的树枝形态和视觉刺激反应特性。此外,我们还探索了表达Brn3c或接受Brn3c+神经元输入的大脑核团。我们的分析显示,Brn3c+RGC的数量和RGC类型的多样性比以前报道的要多得多。在发育过程中表达Brn3c的视网膜节细胞在成体中大多数仍为Brn3c阳性,并且全部表达Brn3a,只有约一半的RGC表达Brn3b。遗传的Brn3c-Brn3b交叉点显示了RGC密度增加的区域,从背颞侧延伸到视网膜腹侧,并与小鼠双眼视野重叠。此外,我们还报告了Brn3c+RGC向丘脑网状核(TRN)的投射,这是一个以前没有显示过接受视网膜输入的视觉核团。此外,Brn3c+神经元突出了以前未知的中脑深核(DpMe)的细分。因此,我们新产生的等位基因为RGC类型分类、脑连接和细胞结构提供了新的生物学见解。
Members of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell types (RGCs), the main transducers of visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing Alkaline Phosphatase (AP) and intersectional genetics had identified three types of Brn3c positive (Brn3c+) RGCs. Here, we describe a novel Brn3cCre mouse allele generated by serial Dre to Cre recombination and use it to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus response properties of Brn3c+ RGC types. Furthermore, we explore brain nuclei that express Brn3c or receive input from Brn3c+ neurons. Our analysis reveals a much larger number of Brn3c+ RGCs and more diverse set of RGC types than previously reported. Most RGCs expressing Brn3c during development are still Brn3c positive in the adult, and all express Brn3a while only about half express Brn3b. Genetic Brn3c-Brn3b intersection reveals an area of increased RGC density, extending from dorso-temporal to ventro-lateral across the retina and overlapping with the mouse binocular field of view. In addition we report a Brn3c+ RGC projection to the thalamic reticular nucleus (TRN), a visual nucleus that was not previously shown to receive retinal input. Furthermore, Brn3c+ neurons highlight a previously unknown subdivision of the deep mesencephalic nucleus (DpMe). Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity and cytoarchitectonic.
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