Gene regulatory switches

The control units of developmental episodes are transcription factors and their cis-regulatory elements capable of integrating developmental signals. They form evolutionary conserved building blocks for animal development and, when misregulated, are often involved in human disease including various forms of cancer.

Particularly interesting are transcription factors capable of switching between transcriptional activation and repression that allows binary cell fate choice upon cell division. Notably, repressive function could add regulative possibilities such as repression checkpoints or developmental pausing for diversification of cell fate.

We have observed switching behaviour for the three transcription factor families (ETS, GATA and TCF) crucially involved in early ectoderm patterning in ascidians.

The ascidian pluripotent ectoderm is particularly suitable to study transcriptional switching mechanisms in vivo as binary events for building precursor of mesendoderm vs. ectoderm, or epidermal vs. neural and/or neurosensorial cells is known with cellular resolution. Furthermore, the precicely spaced and timed activation of direct target genes of above transcription factors and knowledge of corresponding regulatory regions provides an entry point for deciphering the regulatory switching behaviour as activators or repressors.

We use the simplicity of Ciona intestinalis (genomic non-redundancy, fixed lineage and electroporation technique) to learn in depth about the funtions of these evolutionary conserved molecules in vivo, and especially about their less analysed, partially novel role as cell fate switches.

This topic is subject to a PhD thesis for Willi Kari (ÖAW and UIBK funding) and a master thesis for Johannes Will. The projects were partially begun in Patrick Lemaire’s lab at IBDM, Marseille, France (now CRBM, Montpellier), collaboration also with Mike Gilchrist, Crick Institute London, UK.

We collaborate with Vincent Bertrand, IBDM, France, on novel aspects of TCF function.

Ascidian bioadhesion

Freeswimming ascidian larvae produce adhesives when settling at the beginning of metamorphosis to form sessile adults. Consequently, ascidians are major biofoulers threatening marine shipping and food industries.

To define their adhesive properties we describe the ascidian larval adhesive organs and integrate knowledge about its stepwise building from neurectoderm in molecular terms. We isolate candidate genes by transcriptomics, proteomics and functional genomics and test their role in adhesive organ formation and adhesive production. Our research may contribute to the design of both, industrial anti-fouling reagents and, medically relevant tissue compatible glues.

Collaboration with Peter Ladurner, UIBK: co-supervision of PhD student Julia Wunderer (funding Südtiroler Stipendium), MASS-Spec and NGS (Markus Lindner, MUI and ETH Zürich) and Willi Salvenmoser, UIBK. Further collaborations with Daniel Sobral, Gulbenkian Institute, Portugal (differential transcriptomics) and Roberta Pennati, University Milan, Italy. Additional funding: EU-COST Action TD0906 Biological adhesives.

Ascidian adults on boat hull and larva with attachment organ

Members of this workgroup are