Workshop 1: The Biological Challenges in Morphogenesis
Evolution is the filtering of development by ecology (Van Valen 1973, Marshall 1995). However, while the role of ecology in the "selection of the fittest" has a rich and productive history of study, the role of development in the "generation of the fittest" remains much less well known. The primary research goals of the Sears Lab are to determine how development has evolved to generate new morphologies, and the degree to which the nature of development itself biases morphological evolution. To pursue these goals, the lab integrates study across biological fields and temporal scales, from study of genetic processes within individuals to paleontological study of events occurring within lineages over millennia. In her talk, Dr. Sears will highlight ongoing lab research on the mammalian limb that utilizes this integrative approach, and discuss the insights into the role of development in the â€œgeneration of the fittestâ€? that this research has generated. Dr. Sears will also touch on current and future research on the evolution of the mammalian middle ear and dental and sensory adaptations of bats.
Many crucial events that regulate the development of the Drosophila wing, including junctional tension, growth control and planar cell polarity, are concentrated in the apical region of the wingâ€™s epithelial cells. In recent years my laboratory has centered much of its work on these apical events, and especially the role of the apically localized protocadherins Fat and Dachsous and their downstream effectors. However, we have also been examining the roles of the basal end of these cells, which are equally critical for various signaling and morphogenetic events. I will present data on the basal extracellular matrix, the extracellular matrix metalloproteinases, and the basal cell processes of imaginal discs and pupal wings. and discuss new data about their ability to regulate BMP signaling, wing disc morphogenesis, and the peculiar basal-to-basal tubulogenesis of wing vein formation.
The cuticular exoskeleton of insects such as Drospophila is decorated with a variety of structures. Some of these are sensory (e.g. sensory bristles) while others are not innervated (e.g. cuticular hairs or trichomes). Much of the cuticular surface is covered by hairs and in any body region these display a consistent planar polarity. This has best been studied on the wing where each epithelial cell produces a single distally pointing hair. The initial development of each hair is formed by a cytoskeletal mediated outgrowth that forms at the distal edge of each cell. The proteins of the fz/stan pathway that regulates this all accumulate asymmetrically in wing cells prior to hair outgrowth. A number of models have been suggested to explain how this pathway restricts the activation of the actin cytoskeleton to the distalmost part of the cell. These and the evidence for multiple factors influencing the activation of the cytoskeleton will be discussed.
The cuticle of many insects is highly hydrophobic. For example, when a Drosophila wing is dropped into water is not only floats it does not wet. Two factors, surface structures (e.g. hairs) and the waxy coating of the cuticle have been suggested to be important for hydrophobicity. We have found that the wing does not become hydrophobic until shortly before the adult ecloses well after hair morphogenesis and the basis for the lipid coating of the cuticle will be discussed.
Normal blood flow conditions during embryonic development are essential for proper heart formation. Altered blood flow in animal models leads to congenital heart defects that recapitulate those in babies with congenital heart disease, and those in animal models with genetic manipulations. How blood flow alters developmental programs leading to heart defects is not well understood. Our studies show that both early cardiac remodeling in response to altered blood flow and the resulting cardiac defects depend on the degree of blood flow perturbation during embryonic developmental stages. Altered blood flow, therefore, is an important player in the development of congenital heart defects. In this talk we will explore possible consequences of our findings.
Axis extension in vertebrates serves to convert a sphere or disk of cells in the early embryo into a long body plan that resembles that of the adult. By contrast with later morphogenetic movements that shape complex 3D structures, axis extension proceeds as a relatively simple rearrangement of cells in the plane. However, movements are coordinated between multiple layers of mesenchymal and epithelial cells, each undergoing independent rearrangements, and the extracellular matrices that form at their interfaces. Using the elongating dorsal tissues of the Xenopus embryo, our group has developed a complete set of experimental tools and theory for direct biomechanical analysis of these movements. In this presentation I will discuss several surprising findings as we test the coupling between the processes that generate forces needed for extension and the processes that regulate spatial and temporal mechanical properties of the embryo. Forces and material properties can be coupled in a positive fashion that preserves rates of morphogenesis or can be negatively coupled to alter rates of morphogenesis in response to changing environmental conditions. Both mechanisms highlight basic elements of robust control networks that couple mechanics and cell signaling pathways and underlie morphogenetic programs that drive self-assembly.
Understanding how genetic variation acts through development to produce morphological variation is a central challenge in developmental biology. The relationship between genotype and phenotype is both complicated and simplified by development. Canalization, or the suppression of the phenotypic effects of genetic variants and gene interactions greatly complicate the genetics of complex traits, confounding prediction of variation. On the other hand, integration, or the tendency for development to produce correlated variation, simplifies genotype-phenotype maps. This is because integration reflects the convergence of multiple genetic influences on processes that produce coordinated variation among morphological traits. This talk reports results from our work on the developmental-genetic basis for variation in craniofacial form.
Enclosing the gut and it derivatives within the coelom is an essential and universal process of vertebrate embryogenesis. This morphogenesis occurs as somitic and lateral plate mesoderm populations interact forming a muscular body wall that fuses at the ventral mid line. The dynamic boundary between somites and LPM is called the lateral somitic frontier (LSF), and it separates the primaxial (entirely somitic) from the abaxial (somitic cells in lateral plate mesenchyme) domain (Burke&Nowicki, 2003). Changes of cell behavior at the frontier are a large component of anterior-posterior patterning, and have been primarily studied in the limb/fin buds. Extensive data on limb/fin development are placed in contrast to the flank, though few studies have directly addressed the development of flank body wall. We have mapped the LSF in the body wall of embryos representing a range of vertebrate crown groups, finding both commonalities and differences in the process of closing the body wall. Changes in the topography of the frontier and the proportion of primaxial and abaxial domains are correlated with major locomotor adaptations.
The two-galectin tetrapod limb patterning network: synergies of experiment, modeling, and phylogenomicsStuart Newman
(1) The race is not always to the swift. (Still, that's where the smart money is.)
(2) Mathematical and physical models are abstractions, and, as such, always leave something out. Sometimes leaving the parts out is critical for the functioning of the model and can be regarded as extraneous. In other cases, that which is left out is critical to the phenomenon being modeled, and leaving it out causes problems in relating the model to observed reality.