A model of epithelial invagination driven by collective mechanics of identical cells.
Hocevar Brezavscek, A., Rauzi, M., Leptin, M. & Ziherl, P.
Biophys J. 2012 Sep 5;103(5):1069-77.
We propose a 2D mechanical model of a tubular epithelium resembling the early Drosophila embryo. The model consists of a single layer of identical cells with energy associated with the tension of cell cortex. Depending on the relative tension of the apical, basal, and lateral sides of the cells, tissue thickness, and the degree of external constraint, the minimal-energy states of the epithelial cross section include circular shapes as well as a range of inward-buckled shapes. Some of the solutions are characterized by a single deep groove, which shows that an epithelium consisting of cells of identical mechanical properties can infold. This is consistent with what is seen in embryos of certain Drosophila mutants. To ensure that the infolding occurs at a predetermined section of the epithelium, we extend the model by increasing the cross-sectional area of a subset of cells, which is consistent with observations in wild-type embryos. This variation of cell parameters across the epithelium is sufficient to make it fold at a specific site. The model explores previously untested minimal conditions for tissue invagination and is devoid of specificity needed to accurately describe an in vivo situation in Drosophila.
A role for Traf4 in polarizing adherens junctions as a prerequisite for efficient cell shape changes.
Mathew, S.J., Rembold, M. & Leptin, M.
Mol Cell Biol. 2011 Dec;31(24):4978-93. doi: 10.1128/MCB.05542-11. Epub 2011 Oct10.
Apical constriction of epithelial cells is a widely used morphogenetic mechanism. In the Drosophila embryo, the apical constrictions that internalize the mesoderm are controlled by the transcription factor Twist and require intact adherens junctions and a contractile acto-myosin network. We find that adherens junctions in constricting mesodermal cells undergo extensive remodeling. A Twist target gene encoding a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family, Traf4, is involved in this process. While TRAFs are best known for their functions in inflammatory responses, Traf4 appears to have a different role, and its mechanism of action is poorly understood. We show that Traf4 is required for efficient apical constriction during ventral furrow formation and for proper localization of Armadillo to the apical position in constricting cells. Traf4 and Armadillo interact with each other physically and functionally. Traf4 acts in a TNF receptor- and Jun N-terminal protein kinase (JNK)-independent manner to fine-tune the assembly of adherens junctions in the invaginating mesodermal cells.
A genetic in vivo system to detect asymmetrically distributed RNA.
Jayanandanan, N., Gavis, E.R., Riechmann, V. & Leptin, M.
EMBO Rep. 2011 Sep 16. doi: 10.1038/embor.2011.178.
Many RNAs show polarized or otherwise non-random subcellular distributions. To create a method for genome-wide genetic screens for RNAs with asymmetric subcellular distributions, we have combined methods for gene tagging and live imaging of messenger RNA (mRNA). A pilot screen in a highly polarized, differentiated cell in the Drosophila larva, the branched terminal cell of the tracheal system, demonstrates the feasibility of the method for identifying new asymmetrically localized mRNAs in vivo.
Control of Drosophila gastrulation by apical localization of adherens junctions and RhoGEF2.
Kolsch, V., Seher, T., Fernandez-Ballester, G.J., Serrano, L. & Leptin, M.
Science. 2007 Jan 19;315(5810):384-6.
A hallmark of epithelial invagination is the constriction of cells on their apical sides. During Drosophila gastrulation, apical constrictions under the control of the transcription factor Twist lead to the invagination of the mesoderm. Twist-controlled G protein signaling is involved in mediating the invagination but is not sufficient to account for the full activity of Twist. We identified a Twist target, the transmembrane protein T48, which acts in conjunction with G protein signaling to orchestrate shape changes. Together with G protein signaling, T48 recruits adherens junctions and the cytoskeletal regulator RhoGEF2 to the sites of apical constriction, ensuring rapid and intense changes in cell shape.