RRC ID 54988
Author Wang J, Yin Y, Lau S, Sankaran J, Rothenberg E, Wohland T, Meier-Schellersheim M, Knaut H.
Title Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs.
Journal 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.
Volume 46(6)
Pages 751-766.e12
Published 2018-9-24
DOI 10.1016/j.devcel.2018.07.015
PII S1534-5807(18)30600-2
PMID 30122631
PMC PMC6157010
MeSH 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*
IF 9.19
Times Cited 5
Zebrafish Tg(6xTcf/LefBS-miniP:d2EGFP)