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Current Biology
Article . 2004
License: Elsevier Non-Commercial
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Current Biology
Article . 2004 . Peer-reviewed
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Endocytosis Controls Spreading and Effective Signaling Range of Fgf8 Protein

Authors: Michael Brand; Steffen Scholpp;

Endocytosis Controls Spreading and Effective Signaling Range of Fgf8 Protein

Abstract

Secreted signaling molecules released from a restricted source are of great importance during embryonic development because they elicit induction, proliferation, differentiation, and patterning events in target cells . Fgf8 is a member of the fibroblast growth factor family with key inductive functions during vertebrate development of, for example, the forebrain , midbrain , cerebellum , heart , inner ear , and mesoderm . However, the mechanism by which the signaling range of Fgf8 is controlled in a field of target cells is unknown. We studied Fgf8 as a potential morphogen in the nascent neuroectoderm of living zebrafish embryos. We find that spreading of epitope-tagged Fgf8 through target tissue is carefully controlled by endocytosis and subsequent degradation in lysosomes, or "restrictive clearance," from extracellular spaces. If internalization is inhibited, Fgf8 protein accumulates extracellularly, spreads further, and activates target gene expression over a greater distance. Conversely, enhanced internalization increases Fgf8 uptake and shortens its effective signaling range. Our results suggest that Fgf8 spreads extracellularly by a diffusion-based mechanism and demonstrate that target cells can actively influence, through endocytosis and subsequent degradation, the availability of Fgf8 ligand to other target cells.

Related Organizations
Keywords

Embryo, Nonmammalian, Agricultural and Biological Sciences(all), Fibroblast Growth Factor 8, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Carbocyanines, Zebrafish Proteins, Models, Biological, Endocytosis, DNA-Binding Proteins, Fibroblast Growth Factors, Microscopy, Electron, Protein Transport, Ectoderm, Animals, Zebrafish, Signal Transduction, Transcription Factors

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    108
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
108
Top 10%
Top 10%
Top 10%
hybrid