Cell Signalling [be sure to review the figures in your text and those from lecture] 1. The coordination of cellular activities is an essential element during development because it allows a coordinated and regulated unfolding of the information contained in each cell's DNA. 2. This coordination is achieved through a molecular system of signals and receptors which act as information processors. 3. Signalling molecules are either secreted or displayed by cells. They convey information about the state of the cells that secrete them as well as instructions for the behaviour of other cells. 4. Receptors have a basic structure that allows them to recognize signals and to relay the information contained in them to the cell. This is usually achieved through conformational changes, that may be associated with an enzymatic activity. 5. The interactions between signals and receptors can be modulated by other molecules that interfere in a positive or negative way with the informational exchange. 6. The programs of gene expression determine dynamic distributions of signals and receptors during development that contribute to the generation of pattern. 7. Signalling molecules, receptors, and transcription factors are key players in the information processing that underlies the unfolding of the developmental program, and in the coordination of the program in different cells. 8. These elements function as components of signal transduction pathways that are linked and integrated to form information-processing networks. 9. The components of signal transduction networks use molecular currencies (such as second messengers and phosphorylation) to exchange information, and their activities are linked through conformational changes and interactions involving specinc molecular interfaces. Some of these molecular interfaces are used to group sets of signal transduction elements into functional complexes, or to localize them to specific cellular compartments. 10. Some signalling routes from the cell surface to the nucleus employ only a few signal transducers, while others involve multiple intermediaries or use second messengers, offering many opportunities for interactions with other pathways. 11. Signal transduction networks are subject to complex regulatory mechanisms that can be effected, for example, by changes in the concentration, activity or stability of signalling components,or in their compartmentalization within the cell. Feedback control systems are particularly important. 12. Integration of signalling pathways can occur in the nucleus but also at the level of the signal transduction networks and even at the cell surfacce. [Signalling, by a number of growth factors has been shown to be regulated by specific proteoglycans, and it may be that most if not all growth factors may be sequestered at the cell surface by these ECM molecules. For example, binding of FGF to a heparan sulphated proteoglycan, called syndecan, is required for signalling by FGF, and the proteoglycan glycan can bind TGF and present it in high concentration to low-affinity receptors or increase its local concentration in regions where there is little of it.] 13. Cells can respond to different concentrations of the same signalling molecule by activating different genes. If the signalling molecule is secreted from a localized source in a field of cells and can diffuse, it will form a concentration gradient that can be used to pattern the field. Cells will be exposed to different concentrations depending on their distance from the source and will respond by activating different genes. 14. The term 'positional information' refers to the ability of cells to acquire fates depending on their position relative to the source of a diffusible signalling molecule. 15. Morphogens are secreted signalling molecules that can elicit at least 3 different cellular responses in a direct and concentration-dependent manner. 16. The ability of a cell to respond to a signal is called its competence. This can mean the presence of receptors for the signal, the availability of a signal transduction pathway or an open transcriptional state for that signal. 17. A signalling molecule can alter the pattern of response of the target cells by altering their competence (i.e. changing the expression of receptors, state of nuclear activity or modulating the interactions between the signal and the receptor). 18. Gradients of signalling molecules are often used to establish coarse-grained patterns of responses that are refined through interactions between the original signalling molecule and its targets. 19. Short-range signals also play a role in pattern formation and, in vivo, patterns must result from an interplay between long- and short-range signals. (excerpted from MBDB)