Cxcl12 evolution--subfunctionalization of a ligand through altered interaction with the chemokine receptor

Bijan Boldajipour, Maria Doitsidou, Katsiaryna Tarbashevich, Cedric Laguri, Shuizi Rachel Yu, Jonas Ries, Karin Dumstrei, Sylvia Thelen, Julia Dörries, Esther-Maria Messerschmidt, Marcus Thelen, Petra Schwille, Michael Brand, Hugues Lortat-Jacob, Erez Raz

Research output: Contribution to journalArticlepeer-review


The active migration of primordial germ cells (PGCs) from their site of specification towards their target is a valuable model for investigating directed cell migration within the complex environment of the developing embryo. In several vertebrates, PGC migration is guided by Cxcl12, a member of the chemokine superfamily. Interestingly, two distinct Cxcl12 paralogs are expressed in zebrafish embryos and contribute to the chemotattractive landscape. Although this offers versatility in the use of chemokine signals, it also requires a mechanism through which migrating cells prioritize the relevant cues that they encounter. Here, we show that PGCs respond preferentially to one of the paralogs and define the molecular basis for this biased behavior. We find that a single amino acid exchange switches the relative affinity of the Cxcl12 ligands for one of the duplicated Cxcr4 receptors, thereby determining the functional specialization of each chemokine that elicits a distinct function in a distinct process. This scenario represents an example of protein subfunctionalization--the specialization of two gene copies to perform complementary functions following gene duplication--which in this case is based on receptor-ligand interaction. Such specialization increases the complexity and flexibility of chemokine signaling in controlling concurrent developmental processes.

Original languageEnglish
Pages (from-to)2909-14
Number of pages6
Issue number14
Publication statusPublished - Jul 2011


  • Amino Acid Substitution
  • Animals
  • Cell Line
  • Cell Movement
  • Chemokine CXCL12
  • Evolution, Molecular
  • Gene Knockdown Techniques
  • Germ Cells
  • Humans
  • In Situ Hybridization
  • Microscopy, Confocal
  • Receptors, CXCR4
  • Spectrometry, Fluorescence
  • Zebrafish


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