The major aim of our research is to gain a better understanding of how epithelial organs reach and maintain their three-dimensional shape. The underlying morphogenesis processes are regulated by cellular interactions and by the developmental histories of the participating cells. To study cell signalling, we concentrate on two signalling pathways, the Dpp/Bmp and the Fgf pathway. To study the process of morphogenesis, we use the developing tracheal network of the fly and the vascular network of the zebrafish as a model system. Both tissues arise in part through a process called branching morphogenesis, which turns epithelial sheets into tubular networks with distinct features regarding the size, the length and the function of tubes. The branching process is controlled by cell signalling and cell interactions but the consequences of these latter in the responding cells are often poorly understood. Over the years, we have undertaken major efforts to use live imaging in combination with laser ablation to better understand these fascinating morphogenesis processes. We have characterized in detail cell rearrangements during tracheal tube formation in the fly using a GFP fusion protein labelling the Adherens Junctions (AJ) combined with high resolution live imaging, both in wild type and in mutant embryos. To better analyse the branching process at the cellular level, we also developed a single cell imaging approach, and used it to follow wild type or mutant cells during branch formation. We find that complex processes of cell intercalation, which require extensive AJ remodelling, are involved in the formation of branches of different cellular complexities in the trachea, and propose a model of how these cell intercalations occur. We have subsequently used this model to better understand defects in distinct tubes in a number of mutant situations, and tried to define the forces involved in intercalation. These studies attributed important roles for cell signalling in regulating transcription factors; these latter eventually control cell behaviour with regard to cell rearrangements. In addition, our studies point to important roles for apically secreted, luminal proteins in the tubulogenesis process. More recently, we have also started to analyze angiogenesis in zebrafish using similar approaches, with particular emphasis on vessel sprouting and vessel fusion. First interesting results of these studies will also be presented.
Newcastle University (2009) Proc Physiol Soc 16, SA4
Research Symposium: Branching morphogenesis: a closer view using live imaging
M. Affolter1
1. Abteilung Zellbiologie, Biozentrum der Universität Basel, Basel, Switzerland.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.