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5. In vivo molecular measurements of FGF8 morphogen propagation in the zebrafish embryo

Morphogens are signaling molecules which travel across significant distances through the complex network of extracellular matrix to mediate specific cellular responses. Using single molecule Fluorescence Correlation Spectroscopy FCS), we have demonstrated that Fgf8 moves through the extracellular matrix (ECM) by free diffusion and forms a gradient by receptor-mediated endocytosis. Using the biophysical technique of FCS we are further trying to understand how the complex interplay of cell-surface receptors and ECM components regulate the propagation of Fgf8 in a developing zebrafish embryo.

Scientists involved: Mansi Gupta

Related publications:
Scholpp S, Brand M.(2004). Endocytosis controls spreading and effective signaling range of Fgf8 protein. Curr Biol.14(20):1834-41.

Yu, S.R., Burkhardt, M., Nowak, M., Ries, J., Petrášek, Z., Scholpp, S., Schwille, P. and Brand, M. (2009). FGF8 morphogen gradient is formed by a source-sink mechanism with freely-diffusing molecules.  Nature, 461(7263):533-6.

Ries, J. , Yu, S. R., Burkhardt, M., Brand, M. and Schwille, P. (2009). Modular scanning FCS quantifies ligand-receptor interactions in live multicellular organisms. Nature Methods.

Nowak M., Yu SR, Mansi G, Machate A, Brand M (2011) Interpretation of the Fgf8 morphogen gradient is regulated by endocytic trafficking. Nature Cell Biology 13(2):153-158.

Boldajipour, B, Tarbaschevicha K, Doitsidou M, Laguric C, Yu RZ, Riese J, Dumstrei K, Dörries J, Messerschmidt E-M, Schwille P, Brand M, Lortat-Jacobc H, Raz E (2011). A role for biased receptor recognition in chemokine subfunctionalization and evolution. Development 138: 14: 2909-2914.

Müller P, Rogers KW, Yu SR, Brand M, Schier AF. (2013) Morphogen transport. Development. 140(8): 1621-38..

Bökel C, Brand M. (2013) Generation and interpretation of FGF morphogen gradients in vertebrates. Curr Opin Genet Dev.

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