Cell Biology Modeling Development

The fundamental problem of pattern formation for example, how to specify body axes, limbs, digits during development comes down to interpreting a common set of genetic instructions differently at different locations in space (Wolpert 1969). (See Figure 1.1 for an illustration). In all multicellular animals, this process is orchestrated by morphogens, molecules that are produced at discrete sites and disperse to form inspection ration gradients. Such gradients establish patterns because cells are preprogrammed to do very different things at different morphogen concentrations. Each cell responds to morphogens by reading their concentrations, and interprets them through intracellular machineries. A morphogen system usually consists of a region of morphogen-responsive cells, a region of morphogen producing cells, and a set of boundary conditions (Lander 2007). The objective of morphogen-responsive cells is to generate an intracellular signal, the amount of which reflects the level of moprhogen receptor occupancy, to instruct cells to perform their functions or to obtain their fates. A morphogen system often contains: 1) regulated morphogen transport some families of morphogens (Wnts, Hhs) undergo lipid modifications that presumably make them less diffusible and others may undergo active transport (via transcytosis, argosomes, cytonemes, etc); 2) multiple morphogen species Several BMP gradients utilize multiple types of BMP monomers; 3) Multiple morphogen receptor type; 4) nonreceptor binding sites polypeptide morphogens bind to cell surface proteins and/or proteoglycans other than receptors; 5) secreted competitive inhibitors; 6) co-receptors cell surface molecules affect morphogen signaling by acting as co-receptors; 7) extracellular enzymes enzymes cleave inhibitors and co-receptors; 8) feedback regulation feedback regulation of morphogens, receptors, and nonreceptor binding sites; 9) complex feedback loops in intracellular signaling; and along with many other regulations and components (Lander 2007). Here we present a set of basic modeling tools based on a continuum approach for a description of several fundamental biological processes during development. This approach has been successfully