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Intro to Embryology
Organisation of the Body
| Question | Answer |
|---|---|
| What occurs in embryo development | Going from a zygote to an embryo requires repeated divisions to give different cells. Cells must differentiate in the correct area and with the correct shape This occurs via morphogenesis |
| Development of mouse Heart and brain | Using light field and fluorescence imaging we can see that the heart develops above the brain in a mouse This has to move down to its correct location This morphogenic movement converts a flat disc embryo to a 3D organism |
| What can embryology tell us about | Regulation of gene expression Epigenetic control of genes Signalling cascades Cell division e.g. in cancer Cell migration Cytoskeletal function Intracellular transport Organelle function |
| Why study embryos | Cheaper Easier Faster Allows for an understanding of fundamentals |
| When it goes wrong - Congenital defects | Phocomelia caused by Thalidomide Polysyndactyly caused by HOXD 13 mutation Tetralogy of Fallot (life threatening) Sex reversal due to androgen insensitivity |
| Embryos as a model for regenerative medicine | Use an understanding of regeneration in embryos e.g. mouse newborns can regenerate cardio myocytes and Salamanders can regenerate arms, to apply this to humans Cells must know where they are in a limb as only certain areas regrow |
| Study of embryos for iPSC | Understanding embryology allowed for the identification of the correct pluripotency growth factors expressed in an embryo needed to produce iPSCs and to differentiate them into the correct cell |
| Example of differentiation of iPSC | When added to fibroblast growth factor and platelet derived growth factor, stem cells formed glial cells. The same stem cells formed neurons when placed in retinoic acid |
| Vertebrate embryonic development | Comparing Xenopus, chick, mouse and zebrafish. Chick contains the most yolk. All look very different as embryos in size and composition. They reach a phylotypic stage and all look similar (all have Somites) before diversifying again |
| Example of conserved gene function - Pax6 | In human, mouse, zebrafish and drosophila Pax6 controls eye development. Homozygous mutations lead to abnormal formation of the eyes. Pax6 encodes a protein that is similar in shape and function in all organisms |
| Model systems - fly | Cheap and easy but not very similar to humans e.g. no 4 chamber heart Takes 9 days to fully form Initially undergoes nuclei division but no cell division to form a syncytial blastoderm before hatching and undergoing metamorphosis |
| Model systems - mouse | Well understood genetics and similar to humans but more expensive as they are larger, need more food and temperature control Takes around 50 days to reach the adult form |
| Model systems - C elegans | Simple, well understood genetics with cells that always divide the same way to give the same number of cells in each adult Not very similar to humans Takes around 2 days to reach maturity |
| Model systems - Chick | Easy to work with as eggs develop in an incubator Good for 'cut and paste' experiments e.g. changing location of limbs Takes around 60 days to reach maturity |
| Other model systems | Plants Fish (good for genetics) Frogs (large embryo easy to isolate and change) can inject RNA to see its effects |
| Differentiation of cells | Progressive differentiation from a single cell zygote to a Gastrula (in frogs) develops 4 types of tissue Ectoderm Mesoderm Endoderm Germ cells |
| Single Cell sequencing | Can sequence the mRNA in cells to identify which genes are transcriptionally active This can help identify the genes needed to form certain differentiated cells |
| Progressive differentiation | Differentiation occurs via many steps, often involving a pluripotent, multipotent and uni potent cell type E.g. Blood cell differentiation involves pluripotent stem cells, Multipotent hematopoietic stem cells and progenitor cells. |
| Patterning via Morphogen gradients | A morphogen is secreted by a source and diffuses to a sink to form a concentration gradient Different cells respond to different concentrations, so different cells form dependant on their spatial arrangement This is the French flag model |
| Zone of polarising activity | Polarising area secretes morphogens to form a gradient (e.g. sonic hedgehog) In chick limbs high conc forms posterior limb and low conc forms anterior limb To experiment two polarising regions placed in one embryo - mirror image of the pattern occurs |
| What is induction | One group of cells telling another group what to do |
| Organising regions | The region that coordinates development of the embryo When a newt embryo had an extra organiser transplanted in 2 embryos developed |
| Inductive influence of notochord | The Shh in notochord induces a set pattern in dorsal ventricular spinal cord When the Shh moves to the floor plate and BMP4 to the roof plate this forms opposing gradients that trigger neurons to form different levels |
| Epithelial to Mesenchymal tissues | The transition from bonded, held together cells in epithelial to free moving mesenchyme cells E.g. in pluripotent apoplast - epithelium undergoes EMT to form mesoderm This allows epithelial cells to move around the body |
| Mesenchymal to Epithelial tissues | Mesenchymal cells come together and condense into tubules (e.g. to form glomeruli in the kidney) |
| Branching morphogenesis | Kidney morphogenesis - shape given by branching during development Number of branching determines number of nephrons - important in filtering blood |
| Cell death in digit formation | Apoptosis of tissues between digits forms the separated toes of a chick In ducks this does not occur, so they end up with webbed feet |
| Time dependant morphogenesis | Different parts of the body develop at different rates e.g. limbs develop slower than the head This leads to the proportions of babies and adults being very different |
| Conserved molecular models - signalling pathways | Lots of signalling pathways are highly conserved E.g. Sonic hedgehog receptor which leads to changes in molecules in the cytosol and the nucleus E.g. EGF receptor which leads to a cascade reaction inside the cell to control gene expression |
| Reuse of signalling pathways | Sonic hedgehog signalling pathways is used in both neural tubes and limb buds |
| Homeobox transcription factors | These regulate transcription within the nucleus, so are never found outside They determine segement identity Highly conserved |
| Homeotic transformations | Mutations in HOX genes can lead to mutations in segments E.g. vestigial wing enlarged in flies, legs in place of antenna in flies |
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