Cell-cell signalling and chemotactic cell movement during development

Research

Cell movement plays an essential role in development of multicellular organisms, especially during gastrulation, formation of the nervous system and organogenesis. When not properly controlled it results in severe defects and disease. Cell movement is often guided by gradients of attractive and repulsive signaling molecules (chemotaxis). Important open questions how do cells detect gradients of chemo-attractants/repellents and translate this information directed movement up or down gradients of these signaling molecules. How do chemotactic signaling and cell movement interact to create new tissues? We study these questions in the development of two model organisms, the social amoebae Dictyostelium discoideum and during gastrulation in the chick embryo.

For Dictyostelium there exist rapid and efficient techniques to generate targeted gene disruptions and replacements and this has made Dictyostelium is now a key organism to study the molecular basis of serpentine receptor mediated chemotactic signal transduction. We study the mechanisms of cAMP signal detection, cell polarization and localized transduction of these signals to the actin-myosin cytoskeleton (1) Dictyostelium cells do not only detect and move in response to cAMP signals but they can also amplify and pass on cAMP signals to neighbouring cells, which results in the generation of propagating waves of cAMP (2,3). We study the interactions between wave propagation and cell movement that result in the multicellular development of this organism (4).

We also investigate the role of chemotaxis during gastrulation in higher vertebrates. The movement of mesoderm cells appears to be controlled by positive and negative chemotaxis, during gastrulation in the chick embryo. We have identified members of the fibroblast growth factors (FGF's) that may be involved in controlling the chemotactic movement of mesoderm cells (5). There are also indications that other unknown chemo-attractants play a role. We are now investigating the signaling pathways through which FGF's control migration of mesoderm cells and also search for other chemo-attractants.

Publications

1. Sandersius SA, Chuai M, Weijer CJ, Newman TJ (2011) Correlating cell behavior with tissue topology in embryonic epithelia. PLoS One Apr 29;6(4):e18081.
2. Davidson L, Maccario H, Perera NM, Yang X, Spinelli L, Tibarewal P, Glancy B, Gray A, Weijer CJ, Downes CP and Lesie NR (2010) Suppression of cellular proliferation and invasion by the concerted lipid and protein phosphatase activities of PTEN. Oncogene 29(5):687-697.
3. Vasiev B, Balter A, Chaplain M, Glazier JA and Weijer CJ (2010) Modeling gastrulation in the chick embryo: formation of the primitive streak. PLoS One 5(5):e10571.
4. Chuai ML and Weijer CJ. (2009) Who moves whom during primitive streak formation in the chick embryo. HFSP J 3(2):71-76.
5. Chuai M, Dormann, D, and Weijer CJ. (2009) Imaging cell signalling and movement in development. Semin Cell Dev Biol 20(8):947-55.
6. Weijer, CJ. (2009) Collective cell migration in development. J of Cell Science. 122(18):3215-3223.
7. Yang, XS, Chrisman H and Weijer CJ. (2008) PDGF signalling controls the migration of mesoderm cells during chick gastrulation by regulating N-cadherin expression. Development 135(21):3521-3530.
8. Chuai M, Weijer CJ. (2008) The mechanisms underlying primitive streak formation in the chick embryo.Curr Top Dev Biol.81:135-56.
9. Iimura T, Yang X, Weijer CJ, Pourquié O. (2007) Dual mode of paraxial mesoderm formation during chick gastrulation. Proc Natl Acad Sci U S A. 104:2744-9.
10. Leslie NR, Yang X, Downes CP, Weijer CJ. 2007 PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration. Curr Biol. 17:115-25.
11. Dormann D, Weijer CJ. (2006) Imaging of cell migration. EMBO J. 25:3480-93.
12. Chuai M, Zeng W, Yang X, Boychenko V, Glazier JA, Weijer CJ. (2006) Cell movement during chick primitive streak formation.Dev Biol. 296:137-49.
13. Bukahrova T, Weijer G, Bosgraaf L, Dormann D, van Haastert PJ, Weijer CJ. 2005 Paxillin is required for cell-substrate adhesion, cell sorting and slug migration during Dictyostelium development. J Cell Sci. 118:4295-310.
14. Affolter M, Weijer CJ. (2005) Signaling to cytoskeletal dynamics during chemotaxis. Dev Cell.9:19-34.
15. Cui C, Yang X, Chuai M, Glazier JA, Weijer CJ. (2005) Analysis of tissue flow patterns during primitive streak formation in the chick embryo. Dev Biol. 284: 37-47
16. Dormann D, Weijer G, Dowler S, Weijer CJ. (2004) In vivo analysis of 3-phosphoinositide dynamics during Dictyostelium phagocytosis and chemotaxis.J Cell Sci.;117:6497-509.
17. Dormann, D. and C.J. Weijer (2001) Development, 128: 4535-43.
18. Patel, H. et al (2000) Embo Journal, 19: 2247-2256.
19. Dormann, D. et al. (2001) Development, 128: 1081-1088.
20. Yang, X. et al (2002) Dev Cell, 3: 425-437.
21. Dormann, D. et al (2002) Curr Biol, 12: 1178-88.