BK1 Sunday, 5 October 2014 9:18 AM Brian Key: "set a very general frame" What is developmental Biology? - We are interested in animals (NOT plants) => Organisation of cells into functional units through spatial and temporal expression of genes in specific microenvironments Therefore, Jurassic Park is impossible. We could not put human DNA into a chicken's egg and get a human. It is the wrong microenvironment. What can DB be used for ? - Inducing new tissue formation, such as converting skin fibroblasts into functional neurons (replacing the neurons affected in Alzheimer's) - No good animal, in vitro or any kind of model for Alzheimer's. Therefore we should try to build our own model. Build a nervous system and analyse that and see how it could be repaired. What signalling molecules can be interrupted? What is the major driving force for development? · Differential gene expression in space and time - The default state of genes is a repressed state (genes are in chromatin = DNA and protein) . Everything is tied up, beads coiled up. very difficult to access the genes Differential gene expression: · INDUCTION e. g. mesoderm - group of cells or tissues become committed and this involves inducers. The first events of development are inductive events: mesoderm, endoderm and ectoderm - primary germ layers (not to be confused with oocytes and sperm) . REGIONALISATION of tissue e. g. in CNS the brain and spinal cord regions are formed (involves morphogens - genesis of shape) Body axis formation. First the germ layers need to be produced and then different parts of the whole body need to made from these three Layers. · Differentiation of specific cell types/phenotypes within regions involving growth factors (sometimes morphogens are growth factors and vice versa), etc. This is done through gene expression - different morphology and phenotype . Growth factors are typically soluble. Not membrane bound. Diffuse. Therefore different groups of cells can have profound effects on other cells over distances. Cell surface receptors by the recipients have to be expressed. What are the major questions ? - IDENTITY ( how do you make a particular type of tissue; how do you give a particular group an identity? e. g. hands vs feet) - SIZE - SHAPE (MORPHOGENESIS) => for each of the tissues it is vital to understand these three processes in order to attempt to understand to maintain and even repair it Identity - how do you decipher the molecular basis of tissue identity? + observe the tissue! Replay development at our leisure - film it and watch it. We are looking for interactions, relationships, messages, signals = OBSERVE + hypotheses - how was this achieved? To know HOW you need to know WHEN (when are cells determined to differentiate along a specific cell lineage). Cell lineages are very important. C. elegans - always have the same number of cells and a lineage tree can be determined. Each cell is able to be identified to have the same mother,