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

Dev Cell. 2018 Sep 24;46(6):751-766.e12. doi: 10.1016/j.devcel.2018.07.015. | PubMed

John Wang¹, Yandong Yin², Stephanie Lau¹, Jagadish Sankaran³, Eli Rothenberg², Thorsten Wohland³, Martin Meier-Schellersheim⁴, Holger Knaut⁵

1. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
2. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
3. Department of Chemistry, National University of Singapore, Singapore, Singapore.
4. Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
5. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA. Electronic address: holger.knaut@med.nyu.edu.

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.

Presented by John Wang