Control of epithelial morphogenesis in vertebrates

JUAN RAMÓN MARTÍNEZ MORALES

The main focus of our laboratory is to study cellular and molecular mechanisms involved in the morphogenesis of the vertebrate eye. Using zebrafish (Daniorerio) and medaka (Oryziaslatipes) as genetic model systems, we investigate the intrinsic machinery driving the inward folding of the polarized retinal neuroepithelium. Optic cup morphogenesis is an atypical model for epithelial morphogenesis. In contrast to well-known apical constrictions described mainly in Drosophila epithelia, it involves the folding of the tissue towards its basal surface.

Optic cup folding in zebrafish, as revealed in a tg(vsx2.2:GFP-caax) embryo. Imagingstarts at 17 hpf.

Understanding which cellular and molecular aspects of basal constriction are specific of this process, and which are shared with apical constrictions, is therefore one of our long-term objectives. In particular we focus on developmental regulators operating directly on basic cell properties, such as cell adhesion, cell shape or cell contractility. One of these developmental effectors, the transmembrane regulator of integrin endocytosis Opo, has been the subject of several studies in our group. Through a combination of genetic, transcriptomic, bioinformatic and cell biological approaches, we now aim to identify novel components of the molecular machinery involved in optic cup folding. In addition, we are exploring the biophysical aspects of the morphogenetic process using live imaging and mathematical modelling.

A second area of growing interest in the laboratory concerns the evolutionary history of the vertebrate lineage. The analysis of “evo-devo” mechanisms driving the emergence of vertebrate novelties (e.g. the chamber-shaped eye, neural crest, etc), as well as the radiation and stabilization of the vertebrate body plan are also subjects of our research interest. To this end we are taking advantage of the relatively large evolutionary distance (115-200 Myr) between zebrafish and medaka to carry out comparative transcriptomic and genomic analyses. As a long-term perspective, we aim to understand how morphogenetic mechanisms evolve in vertebrates by combining functional genetic studies in fish with computational analyses of vertebrate and invertebrate genomes.

Myosin foci dynamics and basal membrane indentations in 20 hpf control and blebbistatin treated embryos from he line tg(actb1:myl12.1-eGFP)

Projects

In process