Research Group of Dr Marina Mione, Institute of Molecular Oncology Foundation

Research Group of Dr Marina Mione, Institute of Molecular Oncology Foundation

Dr Marina Mione is the leader of the Zebrafish group at the IFOM Fondazione Istituto FIRC di Oncologia Molecolare (The FIRC Institute of Molecular Oncology Foundation) in Milan . Her group use zebrafish to investigate the mechanisms and molecules involved in the control of cell migration.

Studying cell migration in zebrafish offers the advantages of direct visualization of cell movements and ease of embryonic, genetic and molecular manipulation. Individual cell populations can be genetically labelled through the expression of Green Fluorescent Protein (GFP) under the control of tissue or cell specific promoters in transgenic lines. The expression of GFP can be targeted to a specific cell compartment, for example the cell membrane or the cytoskeleton. To visualize the behaviour of the cytoskeleton and intracellular organelles during migration of different cells Marina and her group are generating a number of zebrafish transgenic lines where intracellular organelles and cytoskeletal components are labeled by fluorescent markers.

Two examples of the labelling of cytoskeletal components are provided in the movies (1 and 2) generated using Volocity software. In movie 1 the dynamic localization of an actin binding protein is visualized in vivo through the expression of GFP. Only a few cells express GFP as they were transplanted from a transgenic embryo to a non transgenic one to allow better visualization. In movie 2 all cells express a microtubule binding protein tagged with GFP to allow visualization of the microtubule cytoskeleton during migration and cell division. Both movies were recorded from embryos at the late gastrulation stage, injected with a membrane-bound variant of monomeric red fluorescent protein (mRFP), to visualize cell borders.

One of the main projects in the lab focuses on the role of the reelin pathway in neuronal migration and in the involvement of this pathway in other regulated migrations outside the CNS. Neuronal migration defects in the brain are a major cause of neurodevelopmental disorders and are known to be responsible of devastating human conditions, including mental retardation, autism and epilepsy. The reelin pathway was the first molecular pathway to be identified as responsible for neuronal migration defects in both animal models and human patients.

The group have investigated the role of reelin/dab1 in the migration of the facial motor neurons in the hindbrain, where neuronal migration can be easily visualized and manipulated. Blocking of the pathway induces arrest of neuronal migration, whereas rescue of migration can be obtained with downstream components (see fig.1). This can lead to the development of new therapeutical approaches.

Another focus of the lab is on vascular development and endothelial cell migration. In collaboration with members of the EVGN the lab uses transgenic lines to ease the analysis of the phenotypes induced by perturbing gene function (see fig. 2), as well as molecular, genetic and embryological manipulations to uncover the genetic pathways involved in normal and pathological vascular development.

Marina says "We use Volocity to visualize the dynamic processes that take place in our experiments. 3D rendering allows us to gain a better understanding of the processes we are investigating. Volocity allows us to quickly and easily create movies to share our results with other researchers."

For more information about the Mione Group please visit their lab home page.

Fig. 1: dab1 morpholino blocks the migration of nVII neurons and activation of PI3K rescues it
Fig. 2: Defects in patterning of trunk vessels following injections of morpholino targeting a vascular specific transcription factor.