Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification.
Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification.
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DOI：
10.1371/journal.pone.0076347
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Badea TC
中科院分区：
文献类型：
--
作者：
Shi M;Kumar SR;Motajo O;Kretschmer F;Mu X;Badea TC
视觉信息通过15-20种视网膜神经节细胞（RGC）从视网膜传递到大脑。RGC类型获得其独特的分子，形态，生理和电路特性的发育机制基本上是未知的，但可能涉及组合转录调控。Brn 3转录因子在早期发育阶段的RGC中表达，并且在成人中限于不同的、部分重叠的RGC类型群体。先前，我们描述了Brn 3b（Pou 4f 2）和Brn 3a（Pou 4f 1）对RGC轴突和树突发育的细胞自主作用。我们现在已经研究了Brn 3转录因子之间的遗传相互作用，相对于RGC的发展，通过交叉常规敲除每个Brn 3基因的等位基因与第二个Brn 3基因的条件性敲入报告等位基因，并分析单或双Brn 3敲除对RGC生存和形态的影响。我们发现，Brn 3b损失的结果在Brn 3a阳性RGC的轴突缺陷和树突状乔木面积和层缺陷，并选择性地影响特定Brn 3c（Pou 4f 3）阳性RGC类型的生存和形态。Brn 3a和Brn 3b协同相互作用以控制RGC数目。黑视素阳性ipRGC对组合的Brn 3损失具有抗性，但处于Isll的转录控制下，扩展了RGC特化的组合密码。总之，这些结果完成了我们的知识的转录控制RGC类型规范的机制。他们证明，Brn 3b是正确发育更多RGC细胞类型所必需的，而不是其在成人中的表达模式所暗示的，但几种细胞类型，包括一些Brn 3a，Brn 3c或黑视素阳性RGC是Brn 3b独立的。
Visual information is conveyed from the retina to the brain via 15–20 Retinal Ganglion Cell (RGC) types. The developmental mechanisms by which RGC types acquire their distinct molecular, morphological, physiological and circuit properties are essentially unknown, but may involve combinatorial transcriptional regulation. Brn3 transcription factors are expressed in RGCs from early developmental stages, and are restricted in adults to distinct, partially overlapping populations of RGC types. Previously, we described cell autonomous effects of Brn3b (Pou4f2) and Brn3a (Pou4f1) on RGC axon and dendrites development. We now have investigated genetic interactions between Brn3 transcription factors with respect to RGC development, by crossing conventional knock-out alleles of each Brn3 gene with conditional knock-in reporter alleles of a second Brn3 gene, and analyzing the effects of single or double Brn3 knockouts on RGC survival and morphology. We find that Brn3b loss results in axon defects and dendritic arbor area and lamination defects in Brn3a positive RGCs, and selectively affects survival and morphology of specific Brn3c (Pou4f3) positive RGC types. Brn3a and Brn3b interact synergistically to control RGC numbers. Melanopsin positive ipRGCs are resistant to combined Brn3 loss but are under the transcriptional control of Isl1, expanding the combinatorial code of RGC specification. Taken together these results complete our knowledge on the mechanisms of transcriptional control of RGC type specification. They demonstrate that Brn3b is required for the correct development of more RGC cell types than suggested by its expression pattern in the adult, but that several cell types, including some Brn3a, Brn3c or Melanopsin positive RGCs are Brn3b independent.
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影响因子：
3.7
作者：
Badea TC;Hua ZL;Smallwood PM;Williams J;Rotolo T;Ye X;Nathans J
通讯作者：
Nathans J
外丛状层中的双极细胞突触上的异位视网膜：与多巴胺能小链氨酸细胞和黑色素蛋白神经节细胞的接触。
DOI：
10.1002/cne.22158
发表时间：
2009-11-10
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Dumitrescu ON;Pucci FG;Wong KY;Berson DM
通讯作者：
Berson DM
DOI：
10.1073/pnas.90.22.10841
发表时间：
1993-11-15
影响因子：
11.1
作者：
GERRERO, MR;MCEVILLY, RJ;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
影响因子：
2.7
作者：
Gan, L;Wang, SW;Klein, WH
通讯作者：
Klein, WH
DOI：
10.1523/jneurosci.0901-11.2011
发表时间：
2011-07-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dykes IM;Tempest L;Lee SI;Turner EE
通讯作者：
Turner EE