Hébert Jean M, Lin Mary, Partanen Juha, Rossant Janet, McConnell Susan K
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Development. 2003 Mar;130(6):1101-11. doi: 10.1242/dev.00334.
During development, the embryonic telencephalon is patterned into different areas that give rise to distinct adult brain structures. Several secreted signaling molecules are expressed at putative signaling centers in the early telencephalon. In particular, Fgf8 is expressed at the anterior end of the telencephalon and is hypothesized to pattern it along the anteroposterior (AP) axis. Using a CRE/loxP genetic approach to disrupt genes in the telencephalon, we address the role of FGF signaling directly in vivo by abolishing expression of the FGF receptor Fgfr1. In the Fgfr1-deficient telencephalon, AP patterning is largely normal. However, morphological defects are observed at the anterior end of the telencephalon. Most notably, the olfactory bulbs do not form normally. Examination of the proliferation state of anterior telencephalic cells supports a model for olfactory bulb formation in which an FGF-dependent decrease in proliferation is required for initial bulb evagination. Together the results demonstrate an essential role for Fgfr1 in patterning and morphogenesis of the telencephalon.
在发育过程中，胚胎端脑被划分成不同区域，这些区域会发育成不同的成体脑结构。几种分泌性信号分子在早期端脑的假定信号中心表达。特别是，Fgf8在端脑前端表达，据推测它沿前后（AP）轴对端脑进行模式化。我们采用CRE/loxP基因方法来破坏端脑中的基因，通过消除FGF受体Fgfr1的表达，直接在体内研究FGF信号的作用。在Fgfr1缺陷的端脑中，AP模式化基本正常。然而，在端脑前端观察到形态学缺陷。最显著的是，嗅球不能正常形成。对端脑前部细胞增殖状态的检查支持了一种嗅球形成模型，即最初的嗅球外翻需要FGF依赖的增殖减少。这些结果共同证明了Fgfr1在端脑模式化和形态发生中的重要作用。
