FGF8 acts as a classic diffusible morphogen to pattern the neocortex
| Autor: | Jennifer Wilcoxon, Polina Feldman, Elizabeth A. Grove, Albert Taylor, Stavroula Assimacopoulos, Reiko Toyoda, Tomomi Shimogori, Asuka Suzuki-Hirano |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
animal structures
Fibroblast Growth Factor 8 Body Patterning Fluorescent Antibody Technique Neocortex Biology Fibroblast growth factor Mice FGF8 stomatognathic system medicine Animals Primordium Molecular Biology In Situ Hybridization Microscopy Confocal Cerebrum Electroporation Antibodies Monoclonal Gene Expression Regulation Developmental Immunohistochemistry Receptors Fibroblast Growth Factor Molecular biology Cell biology stomatognathic diseases medicine.anatomical_structure embryonic structures Research Article Developmental Biology Morphogen |
| Zdroj: | Development. 137:3439-3448 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.055392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|