Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs.

Authors:
John Wang
John Wang
School of Medicine
Baltimore | United States
Yandong Yin
Yandong Yin
Peking University
China
Stephanie Lau
Stephanie Lau
University of California at Berkeley
United States
Jagadish Sankaran
Jagadish Sankaran
National University of Singapore
Singapore
Eli Rothenberg
Eli Rothenberg
University of Illinois at Urbana-Champaign
United States
Thorsten Wohland
Thorsten Wohland
National University of Singapore
Singapore | Singapore
Martin Meier-Schellersheim
Martin Meier-Schellersheim
National Institutes of Health
United States
Holger Knaut
Holger Knaut
New York University School of Medicine
United States

Dev Cell 2018 09 16;46(6):751-766.e12. Epub 2018 Aug 16.

Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA. Electronic address:

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.

Abstract Video

Collective cell migration in the Zebrafish lateral line


Source: Cell Press

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http://dx.doi.org/10.1016/j.devcel.2018.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157010PMC

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September 2018
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