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

Zebrafish/growth & development*
Zebrafish/physiology
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Fibroblast Growth Factor 10/genetics
Fibroblast Growth Factor 10/metabolism*
Gene Expression Regulation, Developmental*
Sense Organs/cytology*
Sense Organs/metabolism
Morphogenesis*
Animals
Cell Differentiation
Signal Transduction
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*

(all 15)

PubMed

30122631 Full text @ Dev. Cell

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

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