W3L2Fri Introduction to Development and Cancer Flashcards
Human embryo genesis overview
-From fertilisation to 4 cell stage, more proliferation to morula
-Morula then form into a blastocyst (have a liquid filled internal)
-blastocyst then form the embryo after uterus implantation
Basic idea of development
-Zygotes divide into many cells that are genetically equivalence
-different expression of cells and develop different property
-cells move around and change shape (morphogenesis), differentiate and self-organization of the final body
How can we study gene function in development
Expression analysis:
– which cells express the gene ?
– what is the subcellular location of its gene product?
– how is it regulated by other genes
… transcriptional? post-transcriptional? post-translational?
* Functional (mutant) analysis
– what happens when the gene is mutated?
– what if it’s ectopically expressed?
– What role do different parts of the protein play
Achondroplasia caused by FGFR allele
- > 99 percent of cases caused by FGFR3 G380R mutation.
- Constitutively activated Fibroblast Growth Factor Receptor
- FGF signaling inhibits proliferation of cartilage precursor cells (chondrocytes) so bones fail to grow.
FGF receptor controls cell migration in Drosophila
- Heartless (FGFR) promotes migration of mesodermal cells that form heart tissue
- htl mutants cells fail to spread out and reach dorsal regions (so no heart forms)
link between waardenburg syndrome, neural crest formation and melanoma
-Neural crest cells form by epithelial cells in the neural tube becoming migratory
-They move through the embryo and give rise to many cell types e.g. melanocytes (melanin producing cells)
-Mutations that affect formation or migration of neural crest cells can create areas of the body lacking melanocytes
Mutations can cause melanocytes to become proliferative and migratory (again)– causing melanoma
Differences in gene expression
-housekeeping genes are expressed in all cells
-Other genes are specific to particular types of cells
Making two cells express different genes
- asymmetric division: segregation of intrinsic cell fate determinants
-symmetric division: Cells receive differrent external signals
The cell fate determinant Prospero
Prospero is a transcription factor. When a Drosophila neural stem cell divides, Prospero is segregated to the daughter cell where it controls the fate of the cell.
* It turns on genes associated with neuronal differentiation,
* and turns off genes associated with stem-cell divisions
General paradigm of signalling pathways
-ligand binds to receptor which induces some change in the receptor (e.g. conformation).
* This triggers a sequence of intracellular events, which eventually leads to transcription factors entering the nucleus and regulating gene expression.
What is common signalling pathways
A small set of evolutionarily conserved signaling pathways are used over and over again in developmental processes
Pattern formation
-The process by which a spatial and temporal pattern of cellular activities is organised within the embryo so that a well ordered structure develops
-Pattern formation is achieved by a complex mix of cell-cell signaling, and genetic regulatory networks acting within a cell
Pattern formation via morphogens
-a gradient of concentration (red)
-concentration determines cell fate (different colours)
Morphogenesis
Morphogenesis consists of the many cell behaviours that together help “sculpt” the form of the body
-Occur due to gene expression
Development =
Pattern formation + morphogenesis (+ differentiation)
Pattern formation -The process by which spatiotemporal patterns of gene expression are established
Morphogenesis-The cellular behaviours that help form the body. These are determined by the genes cells express
Differentiation-the process by which cells become specialised due to differential gene expression
