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Characterization of Genes Regulating Growth Factor Signaling and Cytoskeletal Reorganization during Normal and Malignant Development.

Principal investigator; Häcker, Udo, Associate Professor, PhD

Clinical speciality:

Phone: ++46462220864

Co-workers: Martina Schneider, forskare

Higher animal consist of a variety of cell types and tissues. The function of these tissues requires elaborate mechanims for cells to send signals and exchange information. For this purpose cells use secreted signaling molecules, which bind to receptors on the surface of neighboring cells where they can activate intracellular signal transduction cascades. Mutations that disrupt the regulation of these signaling pathways often lead to abnormal development, uncontrolled cell proliferation and cancer. In order to prevent and reverse these malignant developments we must understand the mechanisms regulating the activity of signaling pathways at the molecular level.

The development of multicellular organisms is also associated with extensive morphological rearrangements of tissues. The driving force for these rearrangements is generated by a dynamic reorganization of the actin cytoskeleton. Small GTPases of the Rho-family that are activated by GTP-exchange factors play important roles in this process. Many GTP exchange factors are oncogenes and RGS domain-containing GTP exchange factors, such as DRhoGEF2, may link transforming G-proteins to the GTPase Rho. We study the function of DRhoGEF2-dependent signaling pathways in Drosophila.

A genome-wide sequence analysis has shown that 70% of all human disease genes known to date are conserved in Drosophila. The powerful Drosophila genetic system together with highly developed molecular biology techniques are therefore an excellent tool to investigate the function of individual genes and developmental pathways. The knowledge gained in Drosophila can then be directly applied to vertebrate systems and to the development of methods for treatment and prevention of diseases in mammals and ultimately humans.

Link to project homepage: http://www.med.lu.se/expmed/developmental_biology_in_drosophila

5 recent original publications

Shai Mulinari and Udo Häcker
Hedgehog, but not Odd skipped, induces segmental grooves in the Drosophila epidermis
Development. 2009; Vol. 136: 3875-3880

Shai Mulinari, Mojgan Padash Barmchi and Udo Häcker
DRhoGEF2 and Diaphanous Regulate Contractile Force during Segmental Groove Morphogenesis in the Drosophila Embryo
Molecular Biology of the Cell. 2008; Vol.19: 1883-1892

Padash Barmchi M., Rogers S. and U. Häcker
DRhoGEF2 regulates actin organization and contractility in the Drosophila blastoderm embryo
The Journal of Cell Biology. 2005; Vol. 168(4): 575-585

Häcker U., Nybakken K. and N. Perrimon.
Heparan sulphate proteoglycans: the sweet side of development.
Nature Reviews Molecular Cell Biology. 2005; Vol.6(7): 530-541

Lüders F., Segawa H., Stein D., Selva EM., Perrimon N., Turco SJ. and Häcker U.
slalom encodes a PAPS transporter essential for development in Drosophila.
EMBO Journal. 2003; Vol. 22: 3635-3644

Further publications here (new window)

Financing/year