Spring Selection 2018

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currently open
closes 7 Jan 2018

Research Groups

Portrait Suzanne Eaton

Suzanne Eaton

Cellular mechanisms of epithelial patterning and morphogenesis

Previous and Current Research

My lab is investigating basic mechanisms of patterning and morphogenesis in epithelia – we use the developing wing of drosophila as a model system and apply genetic, cell biological and physical tools to its analysis.

Control of epithelial packing geometry and planar polarity

One focus of the lab is to understand the mechanisms by which epithelial tissues develop specific junctional packing geometries and coordinate the polarity of external structures in the plane. We began to understand that these two processes are linked when we looked carefully at the phenotypes caused by the planar cell polarity (PCP) mutants.  PCP proteins are junctional molecules that polarize their distribution with respect to the proximal distal axis of each cell, forming tightly coupled proximal and distal cortical domains – a process that starts at about 10 hours before hair formation.  The polarity of the PCP domains determines the planar orientation of the emerging wing hairs.  These proteins are required, not only to polarize the orientation of wing hairs, but also to reorganize irregularly packed larval epithelium into an orderly hexagonal one (Classen et al., 2005). They do this at exactly the same time that they develop coordinated polarity within the plane of the epithelium, so we think the two processes are mechanistically related. Using both genetic and cell biological approaches, we have learned that junction remodelling requires an increase in the dynamic endocytosis and recycling of E-Cadherin, and that the PCP proteins influence Cadherin trafficking – possibly by recruiting molecules required for its delivery to the plasma membrane (Classen et al., 2005). The challenge now is to understand the cell biological and physical principles that guide hexagonal repacking, and how they relate to polarization and activity of the PCP proteins.

Lipoproteins in Morphogen signaling

The second focus in the lab is on the role of lipoprotein particles in the trafficking and  signalling of morphogens.  In 2001, we suggested that lipid-linked morphogens spread on particles we called “argosomes” (Greco et al., 2001).  In 2005, we showed that these particles corresponded to lipoproteins: Wingless and Hh associate specifically with the Drosophila lipoprotein Lipophorin (a particle similar to vertebrate ApoB-based lipoproteins).  In addition to the biochemical association, we found that these morphogens co-localized extensively with Lipophorin in endosomes of developing wing epithelial cells.  The association is functionally important, because RNAi-mediated knock-down of Lipophorin reduces long-range Wg and Hh signalling (Panakova et al, 2005).  Ongoing work in the lab is directed at understanding how lipoproteins function in morphogen signalling.
One possible advantage of signalling in the context of a particle, rather than as a free protein, is the potential for additional regulation by other particle-associated proteins.  In support of this idea, we have recently found that Hh signalling can be potentiated by binding of the glypican Dally to the same particles (Eugster et al, 2007).

Suzanne Eaton research: figure
Future Projects and Goals

Control of epithelial packing geometry and planar polarity

While we continue to investigate how PCP proteins regulate membrane trafficking, we have also begun to develop other tools and approaches.  First, we are developing new techniques for long-term time-lapse imaging and automated image analysis that allow us to quantitatively describe the dynamic behaviour of junctions and PCP proteins in wild type and mutant cells. Second, using laser ablation we are studying the balance of forces acting at the junctional region and how it changes during the repacking process and in different mutant backgrounds. Finally, in a collaboration with Frank Jülicher’s group at the Max Planck Institute for the Physics of Complex Systems, we are using these data to develop physical models that will help us understand how local cellular adhesive, elastic and contractile properties are influenced by PCP proteins and other molecules, and how they combine to produce specific packing geometries at a global level.

Lipoproteins in Morphogen signaling

Another interesting possibility is that lipoproteins may influence signalling by delivering specific bioactive lipids.  Using mass spectrometry, we are defining the Lipophorin lipidome to identify molecules of potential interest.  In a complementary approach, we are exploiting the sterol auxotrophy of Drosophila to identify sterol derivatives with important signalling functions.   Finally, understanding these events will require a comprehensive understanding of the molecules and mechanisms that control lipoprotein trafficking in the developing wing.  To this end, we are examining the influence classical lipoprotein receptors, heparan sulfate proteoglycans, as well as lipid-linked morphogens and their receptors on the uptake and subsequent trafficking of these important particles.

Methodological and Technical Expertise
  • Tissue explant culture and long-term imaging
  • Fluorescence spinning disk microscopy
  • Femto-second laser ablation
  • Physical modeling
  • Image processing and analysis
  • Drosophila molecular genetics
  • Lipid and lipoprotein biochemistry
Selected Publications

Eugster, C., Pankova, D., Mahmoud, A. and Eaton, S.
Lipoprotein-Heparan sulfate interactions in the Hedgehog pathway.
Dev. Cell in press. (2007)

Marois, E., Mahmoud, A. and Eaton, S.
The endocytic pathway and formation of the Wingless morphogen gradient.
Development 133:307-17. (2006)

Classen, A, Anderson, K., Marois, E. and S. Eaton.
Hexagonal packing of the Drosophila wing epithelium by the Planar Cell Polarity Pathway.
Dev. Cell 9:1-13 (2005)

Panakova, D., Sprong, H, Marois, E. Thiele, C. and S. Eaton
Lipoprotein particles carry lipid-linked proteins and are required for long-range Hedgehog and Wingless signalling.
Nature 435: 58-65. (2005)

Greco, V. , Hannus, M., and S. Eaton
Argosomes: a potential vehicle for the spread of morphogens through epithelia.
Cell 106:  633-45. (2001)

CV

since 2000
Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden

1997–2000
Staff Scientist at EMBL, Heidelberg

1993–1997
Post-doctoral training at EMBL, Heidelberg

1988–1993
Post-doctoral training at University of California, San Francisco

1988
PhD in Biology, University of California, Los Angeles

Contact

Max Planck Institute of Molecular Cell Biology and Genetics
Pfotenhauerstraße 108
01307 Dresden
Germany

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