Scholpp Steffen, Wolf Olivia, Brand Michael, Lumsden Andrew
MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, London SE1 1UL, UK.
Development. 2006 Mar;133(5):855-64. doi: 10.1242/dev.02248. Epub 2006 Feb 1.
Midway between the anterior neural border and the midbrain-hindbrain boundary, two well-known local signalling centres in the early developing brain, is a further transverse boundary with putative signalling properties -- the zona limitans intrathalamica (ZLI). Here, we describe formation of the ZLI in zebrafish in relation to expression of sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh), and to development of the forebrain regions that flank the ZLI: the prethalamus and thalamus. We find that enhanced Hh signalling increases the size of prethalamic and thalamic gene expression domains, whereas lack of Hh signalling leads to absence of these domains. In addition, we show that shh and twhh display both unique and redundant functions during diencephalic patterning. Genetic ablation of the basal plate shows that Hh expression in the ZLI alone is sufficient for diencephalic differentiation. Furthermore, acquisition of correct prethalamic and thalamic gene expression is dependent on direct Hh signalling. We conclude that proper maturation of the diencephalon requires ZLI-derived Hh signalling.
在前神经边界与中脑-后脑边界(早期发育大脑中两个著名的局部信号中心)之间的中途位置,存在另一个具有假定信号特性的横向边界——丘脑间限制带(ZLI)。在此,我们描述了斑马鱼中ZLI的形成与音猬因子(shh)和刺猬索尼克(twhh)的表达,以及与ZLI两侧前脑区域(前丘脑和丘脑)发育的关系。我们发现增强的Hh信号会增加前丘脑和丘脑基因表达域的大小,而缺乏Hh信号则导致这些区域缺失。此外,我们表明shh和twhh在间脑模式形成过程中既显示出独特功能,也显示出冗余功能。基板的基因消融表明,仅ZLI中的Hh表达就足以实现间脑分化。此外,正确获得前丘脑和丘脑基因表达依赖于直接的Hh信号。我们得出结论,间脑的正常成熟需要ZLI衍生的Hh信号。