Specific role of FGF8 and FGF17 in cortical patterning

描述(申请人提供)：改变胚胎皮质中的FGF8/17信号会导致皮质区域图的重新排列。根据确切的实验条件，在FGF8/17操作之后，个别区域和区域可以缩小或扩大、移位或复制。尽管如此，单个区域的初始形态看起来是正常的；而且，正确的丘脑轴突找到了它们重新定位的目标。我们现在计划检查重新排列大脑皮层区域图的长期影响。我们的总体假设是，随着时间的推移，由于区域地图的早期变化，皮质解剖和功能的变化将会出现。我们期望我们的发现将有助于阐明大脑皮质功能的基本组织是如何在发育过程中建立起来的。我们计划建立一系列小鼠品系，在这些品系中，FGF8/17信号的渐进性丢失会导致前皮质的渐进性减少。这些发现应该进一步表征FGF8/17信号在大脑皮层前-后(A/P)模式中的作用。然后，我们将通过有条件地删除皮质原基中的成纤维细胞生长因子受体基因来确定哪些受体参与了Fgf8/17信号转导。我们的预测是，丢失两个或更多的成纤维细胞生长因子受体将导致Fgf8的表型减少。最后，我们将与突变的小鼠品系杂交，顺序删除编码Emx2、Fgf8、Fgf17的基因中的一个或两个等位基因。这些发现应该有助于确定端脑Fgf8和一些涉及区域模式的转录因子之间的相互作用。

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.