FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis.
FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis.
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DOI：
10.1523/jneurosci.4439-11.2011
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发表时间：
2011-10-26
期刊：
影响因子：
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通讯作者：
Vaccarino FM
中科院分区：
文献类型：
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作者：
Rash BG;Lim HD;Breunig JJ;Vaccarino FM
在发育和进化过程中调节皮质表面积扩张的过程是未知的。我们发现，在皮质发育的最早阶段表达的所有成纤维细胞生长因子受体（FgfR）的功能丧失导致小鼠胚胎第12.5天表面积生长的严重缺陷。在FgfR突变体中，神经元的加速产生导致放射状祖细胞的严重损失和神经发生的过早终止。然而，这些突变体显示出显着的皮质层结构的变化很小。老化实验表明，更大比例的层的命运在早期神经源性阶段产生，揭示FgfR活性通常减缓皮质层命运的时间进展。电穿孔的显性负FgfR在E11.5增加正常小鼠皮层神经发生的影响，同时激活的Notch通路被阻断。结合FgfR突变胚胎中Notch途径基因表达的变化，这些发现表明Notch位于调节皮质神经发生的相同途径中FgfR信号传导的下游，并开始建立调节皮质表面扩张的机制。
The processes regulating cortical surface area expansion during development and evolution are unknown. We show that loss of function of all Fibroblast Growth Factor Receptors (FgfR) expressed at the earliest stages of cortical development causes severe deficits in surface area growth by embryonic day (E) 12.5 in the mouse. In FgfR mutants, accelerated production of neurons led to severe loss of radial progenitors and premature termination of neurogenesis. Nevertheless, these mutants showed remarkably little change in cortical layer structure. Birthdating experiments indicated that a greater proportion of layer fates was generated during early neurogenic stages, revealing that FgfR activity normally slows the temporal progression of cortical layer fates. Electroporation of a dominant negative FgfR at E11.5 increased cortical neurogenesis in normal mice—an effect that was blocked by simultaneous activation of the Notch pathway. Together with changes in the expression of Notch pathway genes in FgfR mutant embryos, these findings indicate that Notch lies downstream of FgfR signaling in the same pathway regulating cortical neurogenesis and begin to establish a mechanism for regulating cortical surface expansion.