Storm Elaine E, Garel Sonia, Borello Ugo, Hebert Jean M, Martinez Salvador, McConnell Susan K, Martin Gail R, Rubenstein John L R
Department of Anatomy, University of California, San Francisco, CA 94143-2711, USA.
Development. 2006 May;133(9):1831-44. doi: 10.1242/dev.02324.
Mouse embryos bearing hypomorphic and conditional null Fgf8 mutations have small and abnormally patterned telencephalons. We provide evidence that the hypoplasia results from decreased Foxg1 expression, reduced cell proliferation and increased cell death. In addition, alterations in the expression of Bmp4, Wnt8b, Nkx2.1 and Shh are associated with abnormal development of dorsal and ventral structures. Furthermore, nonlinear effects of Fgf8 gene dose on the expression of a subset of genes, including Bmp4 and Msx1, correlate with a holoprosencephaly phenotype and with the nonlinear expression of transcription factors that regulate neocortical patterning. These data suggest that Fgf8 functions to coordinate multiple patterning centers, and that modifications in the relative strength of FGF signaling can have profound effects on the relative size and nature of telencephalic subdivisions.
携带低表达和条件性无效Fgf8突变的小鼠胚胎具有小且模式异常的端脑。我们提供的证据表明，发育不全是由Foxg1表达降低、细胞增殖减少和细胞死亡增加所致。此外，Bmp4、Wnt8b、Nkx2.1和Shh表达的改变与背侧和腹侧结构的异常发育有关。此外，Fgf8基因剂量对包括Bmp4和Msx1在内的一组基因表达的非线性影响与全前脑表型以及调节新皮质模式的转录因子的非线性表达相关。这些数据表明，Fgf8起到协调多个模式中心的作用，并且FGF信号相对强度的改变可对端脑亚区的相对大小和性质产生深远影响。
