Dürr Katrin, Holzschuh Jochen, Filippi Alida, Ettl Anne-Kathrin, Ryu Soojin, Shepherd Iain T, Driever Wolfgang
Department of Developmental Biology, Institute for Biology 1, University of Freiburg, Germany.
Genetics. 2006 Oct;174(2):693-705. doi: 10.1534/genetics.105.055152. Epub 2006 Apr 2.
The transcriptional mediator complex has emerged as an important component of transcriptional regulation, yet it is largely unknown whether its subunits have differential functions in development. We demonstrate that the zebrafish mutation m885 disrupts a subunit of the mediator complex, Crsp34/Med27. To explore the role of the mediator in the control of retinal differentiation, we employed two additional mutations disrupting the mediator subunits Trap100/Med24 and Crsp150/Med14. Our analysis shows that loss of Crsp34/Med27 decreases amacrine cell number, but increases the number of rod photoreceptor cells. In contrast, loss of Trap100/Med24 decreases rod photoreceptor cells. Loss of Crsp150/Med14, on the other hand, only slightly reduces dopaminergic amacrine cells, which are absent from both crsp34(m885) and trap100(lessen) mutant embryos. Our data provide evidence for differential requirements for Crsp34/Med27 in developmental processes. In addition, our data point to divergent functions of the mediator subunits Crsp34/Med27, Trap100/Med24, and Crsp150/Med14 and, thus, suggest that subunit composition of the mediator contributes to the control of differentiation in the vertebrate CNS.
转录中介体复合物已成为转录调控的重要组成部分,但在很大程度上尚不清楚其亚基在发育过程中是否具有不同功能。我们证明斑马鱼突变体m885破坏了中介体复合物的一个亚基Crsp34/Med27。为了探究中介体在视网膜分化控制中的作用,我们采用了另外两个破坏中介体亚基Trap100/Med24和Crsp150/Med14的突变体。我们的分析表明,Crsp34/Med27的缺失减少了无长突细胞的数量,但增加了视杆光感受器细胞的数量。相反,Trap100/Med24的缺失减少了视杆光感受器细胞。另一方面,Crsp150/Med14的缺失仅略微减少了多巴胺能无长突细胞,而在crsp34(m885)和trap100(lessen)突变体胚胎中均不存在这种细胞。我们的数据为发育过程中对Crsp34/Med27的不同需求提供了证据。此外,我们的数据表明中介体亚基Crsp34/Med27、Trap100/Med24和Crsp150/Med14具有不同的功能,因此表明中介体的亚基组成有助于脊椎动物中枢神经系统的分化控制。