Dynamics of Development (Minipgm)

in partnership with the Burroughs Wellcome Fund and NIGMS

Coordinators: Eileen Furlong, Michael Levine, Boris Shraiman

Morphogenesis - the process of animal or plant development - involves a fascinating interplay of genetic, biochemical and physical processes that transforms the information encoded in a genome into the shape, size and internal structure of the organism. While recent advances in molecular genetics have uncovered many (and in some cases most) of the important genes and molecular pathways underlying particular aspects of morphogenesis, the link between genes and molecules with macroscopic shapes and structures still remains elusive. Connecting genes and regulatory networks with cellular morphogenesis and macroscopic phenotypes requires understanding (1) the system-wide function of genetic circuits that define cell fates; (2) intercellular interactions and signaling pathways that coordinate growth and differentiation of cells in tissues and defines tissue form and organization. Quantitative analysis has emerged as an essential tool in the study of complex phenotypes associated with development and many aspects of the intercellular interactions central to morphogenesis can be studied and modeled using physics paradigms.

This four-week miniprogram will focus on two rapidly growing and complementary areas of research:

Gene Networks and Cellular Morphogenesis.  During the past 20 years there has been extensive progress in determining the molecular pathways that control the specification of cell identity during animal development.  For select processes such as the patterning of the early Drosophila embryo, detailed circuit diagrams have been elucidated containing the critical regulatory linkages among suites of genes encoding transcription factors and signaling molecules that work in a concerted fashion in development.  However, there is relatively little information concerning how these regulatory networks and signaling pathways control cellular processes such as changes in cell shape, polarity, adhesion, and movement.  A major theme of the proposed workshop is to explore the interface between the regulatory state of a cell and the deployment of the cellular machinery controlling morphogenesis.

Quantitative Imaging and Modeling of “Growth and Form”.  Advances in image acquisition and analysis now permit unprecedented visualization of complex processes that connect cell behavior with morphogenesis on the organismal scale. It is now possible to image in 3D and follow in real time cell growth, division and rearrangement during embryonic or limb and organ development. Live fluorescent imaging allows one to track distribution of key proteins in cells and tissues. For example, it is now possible to image distributions of morphogens that control developmental patterns and directed cell migration in living embryos. Tracking of nuclei and cells combined with localized (with subcellular precision) “laser scalpel” perturbations, allows one to investigate the previously inaccessible role of cell and tissue mechanics in development. Imaging approaches have now been developed for most of the model systems, including Drosophila embryonic and larval development. These methods can be used also with vertebrate embryos applied to the study of defined processes such as, for example, the specification and migration of neural crest. Four-dimensional imaging has greatly expanded the range of developmental phenotypes accessible to study via molecular genetic approaches. It has also changed the “playing field” requiring 1) a new level of quantitative sophistication for characterizing these phenotypes; 2) a new level of complexity of the hypotheses needed to motivate and define new experiments. These new developments set the stage for the emergence of the new approach to theoretical modeling that will seek to quantitatively understand existing observations and make falsifiable predictions that will guide new experiments.