Lec 8: Mechanisms of Development Flashcards
Genes govern cell development
proliferation, specialization, interaction and movement and cell-cell communication
homologous genes can function interchangeably during the development of different species
a gene similar in structure and evolutionary origin to a gene in another species. (eg. a drosophila gene input into a mouse will serve the same function as it did in the drosophila)
Genomic equivalence
all cells contain the same set of genes, the genetic material is identical in every cell but different cells express different sets of genes
Somatic nuclear transfer is a perfect evidence that all cells contain the same genes
it didn’t lose any of the genetic material
How do genes drive development of different tissues when all of the genes are the same in every tissue?
differential gene expression/transcription - where only a small percentage of the genome is expressed in cell type
So like in one cell you will have genes, 1,2,3 but only express gene 1…while in another cell you have the same genes but only express genes 2,3.
Expression of genes at every level
differential gene transcription
• selective nuclear RNA processing
• selective mRNA translation
• differential protein modification
Differential gene expression
RNA localization by in situ hybridization….used to detect mRNA expression in cells or tissues…use a probe to detect where the cells are located
How do you turn on differential gene expression…how do cells know which genes to turn on and which to turn off?
Inducer cells and responder cells. Inducer cells induce other cells but responder cells have the ability to respond…and those that do have the ability to respond are called “competent”
Eg. with tadpole: you need BOTH the inducer and the responder in order to be present in order for eye differentiation to occur.
The optic vesicle is able to trandsuce lens formation in the head ectoderm. However if the optic vesicle is placed in a different loaction (e.g. trunk) that ectoderm will not form a lens. Only the head ectoderm is competent to respond to the signals from the optic vesicle. if the optic vesicle is removed, the surface ectoderm fails to form a normal lens. Other tissues are not able to induce lens formation.
Competence is actively acquired!
Pax6 makes ectoderm competent to respond to inductive signals from the optic vesicle. No PAX6 no eye development. Same in humans
Juxtacrine signaling
physical contact between the inducing and responding cells. Both cells have to be right next to each other
Paracrine signling
no physical contact needed but they are in close proximity.
Morphogens (subset of paracrine) act in a concentrating manner
A morphogen is a paracrine signaling molecule from a source that acts directly on neighborhing cells to produce specific responses that depend on concentration of the morphogen.
Ex. a high conc gradient may direct cells to develop into one pathway vs, a conc gradient in another pathway
The morphogen mechanism and cell response
The cell that is closest to the secreting cell will get higher conc of signaling and will respond differently than another cell which is farther away and is receiving a little less signaling
Signaling cascade shows the stepwise relay of information within a cell. If one of those steps is missing or affected, then the cell
may no longer be competent. You need the entire complex, not just the morphogen
Hedgehog Signaling pathway
SHH is the ligand, it binds Pathched (a Receptor) and this inhibits Smoothened which normally GLI transcription factors
Morphogen gradients in the neural tube
2 competing gradients that set up the doral vantral polarity;
SHH (secreted from floorplate - high at ventral, lower conc towards the dorsal)
BMP (secreted from roofplate - high at dorsal, lower towards ventral. Together the specify different cell types in their exact location
Left right body axis
defects in embryogenesis (heterotaxy) leads to congenital malformations Nodal only on left
Kartagener’s triad: bronchiectasis, infertility and situs inversus (inverted organs)
A clue to initial asymmetry of Nodal expresssion
Clue that ciliary beating controls which way the left-right axis is oriented - embryonic node, the organizer has motile cilia - generates a right to left fluid flow. Cilia generates nodal flow asymmetric. Possibly due to setting up a morphogen gradient - only on the left side of the embryo.
Goal of nodal transcription factor is to turn on PITX2
which is expressed only on the left side
Summary
Pathway used by most vertebrate embryos, same gene in humans
differntial gene expression in lateral plate mesoderm…only expressed on one side not on R side.
Cell cell signaling can turn on itself, its target etc.
Q.1How do somatic nuclear transfer experiments provide evidence supporting the idea of genome equivalence?
Since the nucleus of an adult somatic cell can generate a new adult animal, this indicates no genes were lost during cellular differentiation
Q2. A patient with reversed left-right asymmetry of the heart but otherwise normal arrangement of internal organs would be classified as
heterotaxy
Q3. A morphogen concentration gradient is used to
divide a field of cells by specifying more than one cell type
