LIMA PROVINCIAS

103

The costs of control: Strategies and tradeoffs in robust tissue pattern formation. A. D. Lander1,2, W-C. Lo3, S. Zhou1, P. Zhang2, F. Y. Wan3, Q. Nie3; 1Department of

Developmental and Cell Biology, University of Califorina, Irvine, Irvine, CA, 2Department of Biomedical Engineering, University of Califorina, Irvine, 3Department of Mathematics, University of Califorina, Irvine, CA

One of the principal ways in which long-range tissue patterns are formed is through the actions of gradients of diffusible morphogens. Conserved, complex regulatory mechanisms are found in most morphogen gradient systems, nearly always including elaborate feedback and feed- forward circuits, with contributions by co-receptors, diffusible inhibitors, multiple morphogens, and regulated uptake. As such circuitry is not essential for creating or interpreting morphogen gradients, it has been hypothesized that it evolved to further "strategic" goals—-e.g. robustness, speed, noise-filtering, flexibility, adaptability, etc. Indeed, the ability of some of these mechanisms to contribute, in principle, to the robustness of patterning has been demonstrated mathematically. Yet scarce attention has been paid to the tradeoffs that such strategies incur. For example, it is straightforward to show that strategies for tolerating uncertainty in the rate of morphogen production generally interfere with strategies for overcoming cell-to-cell variability in morphogen response (“spatial noise”), and vice versa. One consequence of such a tradeoff between robustness and noise-tolerance is a limit on the maximum distance over which a morphogen can pattern, a constraint that is indeed observed. Recently, we have begun to systematically identify tradeoffs among strategies for achieving robustness to uncertain production rates of morphogens, receptors and co-receptors. In my talk, I will discuss the general problems of robustness and noise that confront the decapentaplegic (BMP) and wingless (Wnt) morphogen gradients that pattern the Drosophila wing imaginal disc, and introduce the goal of balancing such tradeoffs as a basis for understanding the peculiar regulatory machinery that exists in these gradient systems.

104

Shaping the embryo: Cellular dynamics in development.

J. Zallen1; 1Developmental Biology, Sloan-Kettering Institute/HHMI, New York, NY

A major challenge in developmental biology is to understand how large-scale changes in tissue structure are generated on a cellular and molecular level. A conserved structural feature present in many multicellular animals is a body axis that is elongated from head to tail. This elongation is actively generated in the embryo through spatially regulated cell rearrangements, cell shape changes, and cell divisions. Cell rearrangements provide the driving force for axis elongation in frogs, fish, and chicks. In the fruit fly Drosophila, cell rearrangements cause the embryo to double in length from head to tail and narrow in width from back to front, creating the layout of the body plan. This process is amenable to direct live imaging approaches, which reveal a striking directionality in which large populations of cells align their movements along a common axis. To understand how genes encode the forces that drive these polarized cell behaviors and tissue remodeling, we are using cell biological approaches to identify proteins that are

asymmetrically localized in intercalating cells, large-scale genetic screens to identify the

molecular mechanisms that are required for elongation, and computational methods to analyze cell shape and behavior in three dimensions. We found that proteins involved in cell adhesion and contractile force generation are asymmetrically localized in intercalating cells, where they participate directly in polarized cell behavior. A polarized contractile network provides the global spatial information that guides cell movement, while differential adhesion regulates dynamic interactions between cells. Planar polarized force generation by the contractile actomyosin machinery is regulated by a combination of biochemical signals that establish cell polarity and mechanical feedback systems that coordinate dynamic events between cells. Specifically, we found that nonmuscle myosin II activity not only generates the forces that promote elongation, but myosin localization is also regulated by tension in a mechanism that recruits more myosin to the cortex and propagates contractile behavior from cell to cell. This mechanism triggers a wave of actomyosin contractility that leads to the assembly of multicellular rosette structures that form and resolve directionally, promoting elongation. Rosette behaviors have also been shown to occur in vertebrates and may represent a general mechanism linking single-cell asymmetry to global tissue reorganization.

105

Generating multicellular architecture through collective migration.

D. Gilmour1, E. Dona1, C. Revenu1, G. Valentin1, S. Streichan4; 1Cell Biology and Biophysics,

EMBL, Heidelberg, Germany, 4EMBL

The collective migration of cohorts or tissues is a hallmark of organogenesis, wound repair and many invasive cancers. Cells at the leading edge of migrating collectives display many features characteristic of mesenchyme, such as highly dynamic protrusions and reduced apicobasal polarity, whereas the cells that follow become assembled into canonical epithelia. Thus,

migrating collectives are generated a process that is highly similar to an epithelial-mesenchymal transition (EMT), with the exception that cell-cell junctions are maintained throughout. It is generally unclear how motility and assembly are balanced across migrating tissues. The zebrafish lateral line primordium is a migrating epithelial tissue that becomes assembled into a series of rosette-like mechanosensory organs en route. Previous genetic studies have shown that an extrinsic stripe of the chemokine SDF1 controls the behaviour of ‘leader’ cells at the tissue edge, whereas internal ‘follower’ cells are assembled into epithelial organs through the activity of an internal FGF-signaling circuit. I will present recent work addressing how cell signaling activities and dynamic cell shape changes are integrated during collective migration.

Minisymposium 17: Cell Biology of Micro-Organisms and the Evolution of the