FGF8 acts as a classic diffusible morphogen to pattern the neocortex
FGF8 acts as a classic diffusible morphogen to pattern the neocortex
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DOI：
10.1242/dev.055392
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发表时间：
2010-10
期刊：
影响因子：
4.6
通讯作者：
R. Toyoda;S. Assimacopoulos;J. Wilcoxon;A. Taylor;Polina Feldman;Asuka Suzuki-Hirano;T. Shimogori;E. Grove
中科院分区：
文献类型：
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作者：
R. Toyoda;S. Assimacopoulos;J. Wilcoxon;A. Taylor;Polina Feldman;Asuka Suzuki-Hirano;T. Shimogori;E. Grove
Gain- and loss-of-function experiments have demonstrated that a source of fibroblast growth factor (FGF) 8 regulates anterior to posterior (A/P) patterning in the neocortical area map. Whether FGF8 controls patterning as a classic diffusible morphogen has not been directly tested. We report evidence that FGF8 diffuses through the mouse neocortical primordium from a discrete source in the anterior telencephalon, forms a protein gradient across the entire A/P extent of the primordium, and acts directly at a distance from its source to determine area identity. FGF8 immunofluorescence revealed FGF8 protein distributed in an A/P gradient. Fate-mapping experiments showed that outside the most anterior telencephalon, neocortical progenitor cells did not express Fgf8, nor were they derived from Fgf8-expressing cells, suggesting that graded distribution of FGF8 results from protein diffusion from the anterior source. Supporting this conclusion, a dominant-negative high-affinity FGF8 receptor captured endogenous FGF8 at a distance from the FGF8 source. New FGF8 sources introduced by electroporation showed haloes of FGF8 immunofluorescence indicative of FGF8 diffusion, and surrounding cells reacted to a new source of FGF8 by upregulating different FGF8-responsive genes in concentric domains around the source. Reducing endogenous FGF8 with the dominant-negative receptor in the central neocortical primordium induced cells to adopt a more posterior area identity, demonstrating long-range area patterning by FGF8. These observations support FGF8 as a classic diffusible morphogen in neocortex, thereby guiding future studies of neocortical pattern formation.
