From Genes to Growth and Form
Coordinators: Suzanne Eaton, Madhav Mani, Andrew Oates, and Boris Shraiman
Scientific Advisors: Cassandra Extavour and Joel Rothman
Animal genomes encode elaborate developmental programs, which are executed in the process of morphogenesis. Molecular-genetic study of development has uncovered many, and in some cases most, of the genes that define the adult body plan and control the development. Yet the dynamical process, the "executable program" of development that links genes and molecules on subcellular scale to the resulting macroscopic shapes and structures, remains far from understood. How does the spatio-temporally regulated cell proliferation and differentiation give rise to limbs and organs with correct size, form, and function? Understanding this problem requires identifying the intercellular signals and mechanical interactions that propagate information throughout the tissue and define collective behavior of cells. It is on this mesoscopic scale of intercellular interaction that the bridge between molecules and the large-scale morphology is to be found.
The scientific program will be anchored by the following intersecting themes:
- Role of time in patterning space: will aim to reexamine the scenario of static spatial patterning by a gradient of morphogen concentration, confronting it with the observations of an adaptive response and the hypothesis that cells respond only to the time derivative.
- Interplay of global and local patterning signals: will focus on the relation between local polarization of cell and global anisotropy, examine the extent of global planar cell polarity order in tissues, and reconcile observed local cell deformation with global distribution of mechanical stress.
- Mechanical regulation of growth: will consolidate evidence for mechanical regulation of growth of tissues in different systems and evaluate different approaches to measuring stress in live tissues and monitoring its dynamics. What do we know about the molecular pathways of mechano-regulation?
- Cellular “flows” and their generation: will ask, can we determine the driving forces behind observed cellular flows? We will compare cell-deformation, cell intercalation and cell proliferation as the drivers of global cell rearrangement.
- Polarity and anisotropy in defining tissue morphology: will consolidate existing knowledge on the mechanisms of planar cell polarity (PCP and Fat/Ds pathways) and their role in defining clonal shapes and tissue anisotropy and controlling cellular flows and tissue rearrangement.
- In toto organogenesis: will focus on the few model morphogenetic systems, like Drosophila ovarian development, in which the dynamics of morphogenesis could be examined in its entirety.
- Comparative morphogenesis: will examine the similarities and differences between developmental mechanisms in different limbs and organs, e.g. wing vs leg and eye of Drosophila; and in different animals, e.g. Drosophila versus wasp or beetle.
The program will run side by side with the affiliated SB Advanced School of Quantitative Biology course on “Mechanics and Mechanisms of Morphogenesis,” which will focus on live imaging, quantitative analysis, and phenomenological modeling of developmental processes in a variety of model organisms such as Drosophila, zebrafish, Caenorhabditis elegans and Ciona.
This program is funded by the Gordon and Betty Moore Foundation.