PUBLICATION
Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs
- Authors
- Wang, J., Yin, Y., Lau, S., Sankaran, J., Rothenberg, E., Wohland, T., Meier-Schellersheim, M., Knaut, H.
- ID
- ZDB-PUB-180821-3
- Date
- 2018
- Source
- Developmental Cell 46(6): 751-766.e12 (Journal)
- Registered Authors
- Knaut, Holger, Wang, John
- Keywords
- FGF signaling, Kal1/Anosmin1, Kallmann Syndrome, growth factor diffusion, sensory organ differentiation
- MeSH Terms
-
- Animals
- Cell Differentiation
- Fibroblast Growth Factor 10/genetics
- Fibroblast Growth Factor 10/metabolism*
- Gene Expression Regulation, Developmental*
- Morphogenesis*
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism*
- Sense Organs/cytology*
- Sense Organs/metabolism
- Signal Transduction
- Zebrafish/growth & development*
- Zebrafish/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 30122631 Full text @ Dev. Cell
Citation
Wang, J., Yin, Y., Lau, S., Sankaran, J., Rothenberg, E., Wohland, T., Meier-Schellersheim, M., Knaut, H. (2018) Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs. Developmental Cell. 46(6):751-766.e12.
Abstract
Growth factors induce and pattern sensory organs, but how their distribution is regulated by the extracellular matrix (ECM) is largely unclear. To address this question, we analyzed the diffusion behavior of Fgf10 molecules during sensory organ formation in the zebrafish posterior lateral line primordium. In this tissue, secreted Fgf10 induces organ formation at a distance from its source. We find that most Fgf10 molecules are highly diffusive and move rapidly through the ECM. We identify Anosmin1, which when mutated in humans causes Kallmann Syndrome, as an ECM protein that binds to Fgf10 and facilitates its diffusivity by increasing the pool of fast-moving Fgf10 molecules. In the absence of Anosmin1, Fgf10 levels are reduced and organ formation is impaired. Global overexpression of Anosmin1 slows the fast-moving Fgf10 molecules and results in Fgf10 dispersal. These results suggest that Anosmin1 liberates ECM-bound Fgf10 and shuttles it to increase its signaling range.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping