Frontal cortex subdivision patterning is coordinately regulated by Fgf8, Fgf17, and Emx2.

Frontal cortex subdivision patterning is coordinately regulated by Fgf8, Fgf17, and Emx2.
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DOI:
10.1002/cne.21709
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发表时间:
2008-07-10
影响因子:
2.5
通讯作者:
Rubenstein, John L. R.
Rubenstein, John L. R.
中科院分区:
医学3区
文献类型:
--
作者:
Cholfin, Jeremy A.;Rubenstein, John L. R.

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额叶皮层(FC)在认知、运动和行为中起着重要作用。然而,人们对控制其发展的遗传机制知之甚少。我们最近描述了一组基因表达标记物,其描绘了新生FC亚群并鉴定了Fgf 17 −/−突变小鼠中的FC区域化缺陷(Proc. Natl. Acad. Sci.联合S. A. [in press])。在本研究中,我们应用这个FC基因表达面板来检查Fgf 8 neo/neo,Emx 2 −/−和Emx 2 −/−; Fgf 17 −/−新生小鼠的区域化表型。我们报告,Fgf 8,Fgf 17和Emx 2发挥不同的作用,在分子区域化的FC细分。在区域化的变化预示着不同的影响,吻图案中心FGF 8和FGF 17信号对吻皮质神经上皮细胞,揭示了改变表达的Spry 1,Spry 2,和“吻”转录因子Er 81,Erm,Pea 3,和Sp 8。我们使用Emx 2 −/−; Fgf 17 −/−双突变体提供了直接证据,表明Emx 2和Fgf 17拮抗性调节喙侧皮质神经上皮和FC区域化中Erm,Pea 3和Er 81的表达。我们已经整合了我们的研究结果,提出了一个模型,如何成纤维细胞生长因子调节FC图案通过调节区域内的FC原基转录因子的表达。
The frontal cortex (FC) plays a major role in cognition, movement and behavior. However, little is known about the genetic mechanisms that govern its development. We recently described a panel of gene expression markers that delineate neonatal FC subdivisions and identified FC regionalization defects in Fgf17−/− mutant mice ( Proc. Natl. Acad. Sci. U. S. A. [in press]). In the present study, we applied this FC gene expression panel to examine regionalization phenotypes in Fgf8neo/neo, Emx2−/−, and Emx2−/−; Fgf17−/− newborn mice. We report that Fgf8, Fgf17 and Emx2 play distinct roles in the molecular regionalization of FC subdivisions. The changes in regionalization are presaged by differential effects of rostral patterning center Fgf8 and Fgf17 signaling on the rostral cortical neuroepithelium, revealed by altered expression of Spry1, Spry2, and “rostral” transcription factors Er81, Erm, Pea3, and Sp8. We used Emx2−/−; Fgf17−/− double mutants to provide direct evidence that Emx2 and Fgf17 antagonistically regulate the expression of Erm, Pea3, and Er81 in the rostral cortical neuroepithelium and FC regionalization. We have integrated our results to propose a model for how fibroblast growth factors regulate FC patterning through regulation of regional transcription factor expression within the FC anlage.
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