Directional tissue migration through a self-generated chemokine gradient

Erika Dona, Joseph D. Barry, Guillaume Valentin, Charlotte Quirin, Anton Khmelinskii, Andreas Kunze, Sevi Durdu,

Lionel R. Newton, Ana Fernandez-Minan, Wolfgang Huber, Michael Knop and Darren Gilmour

Nature (2013) 503, 285–289

Speaker: Hsin-I Wang (汪欣儀)                             Time: 15:00~16:00, Oct 15, 2014

Commentator: Dr. Tzu-Fun Fu (傅子芳 博士)              Place: Room 601

Abstract :

Directional collective cell migration is involved in a variety of physiological functions, such as embryonic development, neuronal differentiation, immune function, vascular remodeling and wound healing. It contributes to pathological states, including atherosclerosis, chronic inflammation and cancer (1). Cells can display single and collective migration. Migrating to a special direction, cells are guided by chemokine gradient. For example, the immune cells are attracted by chemoattractants which is released from the infection site (2). Previous studies have shown thatCXC chemokine receptors, such as CXCR4 and CXCR7 are critical in the development and progression of solid tumors. CXCL12, also known as SDF-1, is the ligand of CXCR4 and CXCR7 (3).To visualize the endogenous gradient of chemokine, the authors applied a tandem fluorescent protein timer (-tFT) approach and analyzed the ligand-triggered receptor turnover in living animal. They measured the CXCR4b-tFT lifetime ratio, which indicated the age of protein populations. Fluorescent protein timer is that the newly synthesized proteins show only green fluorescence, but turn to yellow, orange, and finally red over time. In this study, the authors used zebrafish embryo model. In this model, lateral line primordia, a group of cells with collective migration ability, that become a mechanosensory organs during development. They found that the SDF-1 gradient was lost in CXCR7-null mutants. CXCR7 plays an important role in producing chemokine gradient as a directional signal for primordial migration. Based on these results, they conclude that CXCR7 sink activity is required for and sufficient to pattern chemokine activity across the primordium. In addition, the SDF-1 gradient migrating collective cells can determine their own directionality via a self-generated gradient mechanism.

References :

1.     Friedl, P., and Wolf, K. (2010). Plasticity of cell migration: a multiscale tuning model. J. Cell

Biol. 188, 11–19.

2.     Kolaczkowska, E., and Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nat. Rev. Immunol. 13, 159–175.

3.     Anup Kumar Singh, and Dipak Datta, et al. (2013). Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12. Cytokine Growth Factor Rev. 24, 41–49.