Adutwum-Ofosu Kevin Kofi, Magnani Dario, Theil Thomas, Price David J, Fotaki Vassiliki
The University of Edinburgh, Centre for Integrative Physiology, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK.
Department of Anatomy, College of Health Sciences, University of Ghana, Accra, Ghana.
Brain Struct Funct. 2016 Sep;221(7):3709-27. doi: 10.1007/s00429-015-1127-3. Epub 2015 Oct 12.
The mammalian eminentia thalami (EmT) (or thalamic eminence) is an embryonic forebrain structure of unknown function. Here, we examined the molecular and cellular properties of the mouse EmT. We first studied mRNA expression of signalling molecules and found that the EmT is a structure, rich in expression of secreted factors, with Wnts being the most abundantly detected. We then examined whether EmT tissue could induce cell fate changes when grafted ectopically. For this, we transplanted EmT tissue from a tau-GFP mouse to the ventral telencephalon of a wild type host, a telencephalic region where Wnt signalling is not normally active but which we showed in culture experiments is competent to respond to Wnts. We observed that the EmT was able to induce in adjacent ventral telencephalic cells ectopic expression of Lef1, a transcriptional activator and a target gene of the Wnt/β-catenin pathway. These Lef1-positive;GFP-negative cells expressed the telencephalic marker Foxg1 but not Ascl1, which is normally expressed by ventral telencephalic cells. These results suggest that the EmT has the capacity to activate Wnt/β-catenin signalling in the ventral telencephalon and to suppress ventral telencephalic gene expression. Altogether, our data support a role of the EmT as a signalling centre in the developing mouse forebrain.
哺乳动物的丘脑隆起(EmT)(或丘脑突出部)是一种功能未知的胚胎前脑结构。在此,我们研究了小鼠EmT的分子和细胞特性。我们首先研究了信号分子的mRNA表达,发现EmT是一个富含分泌因子表达的结构,其中Wnt的表达量最高。然后,我们检测了EmT组织异位移植时是否能诱导细胞命运改变。为此,我们将来自tau-GFP小鼠的EmT组织移植到野生型宿主的腹侧端脑,这是一个端脑区域,正常情况下Wnt信号不活跃,但我们在培养实验中表明它能够对Wnt作出反应。我们观察到,EmT能够诱导相邻腹侧端脑细胞异位表达Lef1,Lef1是一种转录激活因子,也是Wnt/β-连环蛋白信号通路的靶基因。这些Lef1阳性、GFP阴性的细胞表达端脑标记物Foxg1,但不表达通常由腹侧端脑细胞表达的Ascl1。这些结果表明,EmT有能力在腹侧端脑中激活Wnt/β-连环蛋白信号,并抑制腹侧端脑基因表达。总之,我们的数据支持EmT在发育中的小鼠前脑中作为信号中心的作用。