S. Eaton (MPI-CBG, Dresden), C. Extavour (Harvard), N. Goehring (MRC LMCB, London), P. Lemaire (CRBM, Montpelier), M. Mani (NWU), A. Oates (MRC LMCB, London), A. Pavlopoulos (Janelia, HHMI), B. Shraiman (KITP, UCSB), S. Streichan (KITP, UCSB), A. Warmflash (Rice) and E. Wieschaus (Princeton)
Guest Lecturers (partial list):
This course aims at bringing together the Biology and Physics perspectives on Morphogenesis - the process through which animals and plants acquire their physical form and biological function. Morphogenesis is a developmental program encoded in DNA and kick-started by “maternal factors” in the egg. Developmental Biology has made enormous progress in identifying the genes that specify developmental axes and the general body-plan as well as the numerous genes and biochemical signals that control growth and cell differentiation. Yet, even as we know the expression of what gene would cause a fruit-fly to grow a leg on its head instead of an antennae, we have little understanding of how controlled growth and cell differentiation actually generates the distinct shape and structure that make a leg rather than an antennae. A century ago, before the advent of developmental genetics, D’Arcy Thompson viewed Morphogenesis as an essentially physical process of controlled growth. Revisiting Thomson’s agenda, the challenge is to connect the macroscopic dynamics of morphogenesis to the underlying molecular genetic and cell-biological processes. Physics perspective in particular focuses on the dynamical aspect of morphogenesis. To use a metaphor, what are the “laws of motion” that define the developmental trajectory from maternal factors as “initial conditions” to embryonic structures and beyond? Physics perspective also brings to fore the role of intercellular interactions in coordinating development and, in particular, the role of mechanics alongside with biochemical signals governing collective and individual behavior of cells in tissues.
The course will be anchored by laboratory projects involving different morphogenetic processes in model organisms such as the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, zebra fish (D. rerio), a sea squirt (Ciona) and a crustacean (Parhyale hawaiensis). Experimental projects will aim to introduce quantitative approaches to the study of the dynamics of morphogenesis.
This five-week course will consist of a first "bootcamp" week to be followed by two 2-week research project sessions. Each session will consist of three or four experimental projects led by instructors and TAs who will closely work with groups of 4-5 students. Each day will consist of a morning lecture and discussions followed by lab work late into the evening.
The bootcamp week will be aimed at introducing all students to a basic set of microscopy, quantitative image analysis and theoretical modeling tools that will be necessary for the later research projects. Bootcamp will also introduce students to different laboratory model systems of development.
The course will run side by side (and share review lectures and research seminars) with the KITP workshop "From Genes to Growth and Form", which will provide a fertile forum for discussions and the exchange of ideas with the workshop participants. The scientific program of this workshop will be anchored by the following intersecting themes, which are central to the subject of the course:
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; reconcile observed local cell deformation with global distribution of mechanical stress.
Mechanical regulation of growth: consolidate evidence for mechanical regulation of growth of tissues in different systems. 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: How can we determine the driving forces behind observed cellular flows? Comparison of cell-deformation, cell intercalation and cell proliferation as the drivers of global cell rearrangement.
Polarity and anisotropy in defining tissue morphology: 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 system, like Drosophila ovarian development, where the dynamics of morphogenesis could be examined in its entirety.
Comparative morphogenesis: will examine the similarity 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 vs wasp or beetle.
EXPERIMENTAL PROJECTS (preliminary list)
Suzanne Eaton: Drosophila wing development
Nathan Goehring: C. elegans embryonic development
Patrick Lemaire: Ciona embryonic development
Andy Oates: Zebra fish somitogenesis
Aryeh Warmflash: Stem cell differentiation patterns in vitro
Anastasios Pavlopoulos: Developmental morphogenesis in a crustacean