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Axon guidance relies on a combinatorial code of receptor and ligand interactions that direct adhesive/attractive and repulsive cellular responses. Recent structural data have revealed many of the molecular mechanisms that govern these interactions and enabled the design of sophisticated mutant tools to dissect their biological functions. Here, we discuss the structure/function relationships of four major classes of guidance cues (ephrins, semaphorins, slits, netrins) and examples of morphogens (Wnt, Shh) and of cell adhesion molecules (FLRT). These cell signaling systems rely on specific modes of receptor-ligand binding that are determined by selective binding sites; however, defined structure-encoded receptor promiscuity also enables cross talk between different receptor/ligand families and can also involve extracellular matrix components. A picture emerges in which a multitude of highly context-dependent structural assemblies determines the finely tuned cellular behavior required for nervous system development.

Original publication

DOI

10.1146/annurev-cellbio-111315-125008

Type

Journal article

Journal

Annual review of cell and developmental biology

Publication Date

10/2016

Volume

32

Pages

577 - 608

Addresses

Department of Biochemistry, Oxford University, Oxford OX1 3QU, United Kingdom; email: elena.seiradake@bioch.ox.ac.uk.