Xu Q, Alldus G, Macdonald R, Wilkinson D G, Holder N
DBRC, The Randall Institute, King's College, London, UK.
Nature. 1996 May 23;381(6580):319-22. doi: 10.1038/381319a0.
Early during its development, the vertebrate brain is subdivided into regions that have distinct fates and correlate with the expression domains of regulatory genes, but little is known about the cell-cell interactions that establish this spatial pattern. Candidates for regulating such interactions are the Eph-related receptor tyrosine kinases (RTKs) which have spatially restricted expression in the developing brain. These RTKs may mediate cell-contact-dependent signalling by interacting with membrane-bound ligands, and have been implicated in axon repulsion and the segmental restriction of gene expression in the hindbrain, but nothing is known regarding their function in the rostral neural epithelium. Here we use a dominant-negative approach in the zebrafish embryo to interfere with the function of Rtk1, an Eph-related RTK expressed in the developing diencephalon. We find that expression of a truncated receptor leads to expansion of the eye field into diencephalic territory and loss of diencephalic structures, indicating a role for Rtk1 in patterning the developing forebrain.
在脊椎动物大脑发育早期，它会被细分为具有不同命运且与调控基因表达域相关的区域，但对于建立这种空间模式的细胞间相互作用却知之甚少。调节此类相互作用的候选分子是Eph相关受体酪氨酸激酶（RTK），它们在发育中的大脑中具有空间限制表达。这些RTK可能通过与膜结合配体相互作用来介导细胞接触依赖性信号传导，并已涉及轴突排斥和后脑基因表达的节段性限制，但关于它们在头侧神经上皮中的功能却一无所知。在这里，我们在斑马鱼胚胎中使用显性负性方法来干扰Rtk1的功能，Rtk1是一种在发育中的间脑中表达的Eph相关RTK。我们发现截短受体的表达会导致眼区扩展到间脑区域并导致间脑结构缺失，这表明Rtk1在发育中的前脑模式形成中发挥作用。
