Specific role of FGF8 and FGF17 in cortical patterning

描述（由申请人提供）：改变胚胎皮层中的FGF 8/17信号传导导致皮层区域图重排。根据确切的实验条件，单个区域和区域可以在FGF 8/17操作后缩小或扩大，移位或复制。尽管如此，个别地区的初始形态似乎正常，而且，正确的丘脑轴突找到他们重新定位的目标。我们现在计划检查重新排列皮质区地图的长期影响。我们的总体假设是，随着时间的推移，皮层解剖结构和功能的改变将随着区域图的早期变化而出现。我们希望我们的发现将有助于阐明大脑皮层功能的基本组织是如何在发育过程中建立的。我们计划产生一系列小鼠品系，其中FGF 8/17信号传导的逐渐丧失导致前皮质的逐渐减少。这些发现应进一步表征FGF 8/17信号传导在前-后（A/P）皮质模式中的作用。然后，我们将确定哪些受体参与FGF 8/17信号通过有条件地删除floxed FGF受体基因在皮层primoridum。我们的预测是，两个或多个Fgf受体的损失将表型减少Fgf 8。最后，我们将交叉突变小鼠品系以依次删除编码Emx 2、Fgf 8、Fgf 17的基因的一个或两个等位基因。研究结果应有助于确定端脑FGF 8和一些转录因子之间的相互作用，涉及区域图案。

DESCRIPTION (provided by applicant): Altering FGF8/17 signaling in the embryonic cortex causes a rearrangement of the cortical area map. Depending on the exact experimental condition, individual areas and regions can be shrunken or expanded, shifted or duplicated following FGF8/17 manipulations. Nonetheless, initial morphology of individual areas appears normal; moreover, correct thalamic axons find their repositioned targets. We now plan to examine the long-term effects of rearranging the cortical area map. Our overall hypothesis is that alterations in cortical anatomy and function will emerge over time as a result of early changes in the area map. We expect that our findings will help to shed light on how basic organization of cerebral cortical function is set up in development. We plan to generate a series of mouse lines in which progressive loss of FGF8/17 signaling leads to a progressive decrease in anterior cortex. These findings should further characterize the role of FGF8/17 signaling in anterior-posterior (A/P) patterning of the cortex. We will then determine which receptors are involved in Fgf8/17 signaling by conditionally deleting floxed Fgf receptor genes in the cortical primoridum. Our prediction is that loss of two or more Fgf receptors will phenocopy reduction of Fgf8. Finally, we will cross mutant mouse lines to delete, sequentially, one or both alleles of the genes encoding Emx2, Fgf8, Fgf17. Findings should help identify interactions between telencephalic Fgf8 and some of the transcription factors implicated in area patterning.