Developmental Flashcards
What is epistasis?
Ordering genes into pathways
What is the hedgehog signalling pathway in vertebrates?
Ptc inhibits Smo
Shh inhibits Ptc
Frees up Smo and allows it to activate Gli transcription factor
Gli enters nucleus and activates transcription of target genes
What inhibits Ptc?
Shh
When Ptc is inhibited, what does this do to Smo?
Activates
What occurs to signalling pathways in Basal cell carcinoma?
Mutations that predispose:
- Ptc - loss of function mutation (amorphic) - cannot inhibit Smo so activation of Gli, cell division
- Smo: gain of function mutation (hypermorphic) - overactivity of pathway - cell divisions
What causes APC and colon cancer in terms of signalling pathways?
- Inappropriate activation of Wnt pathway
- Polyps (small tumours) form in colon
What characteristics do tumour cells share with embryonic cells?
- Rapidly dividing
- Undifferentiated
- Undergo epithelial to mesenchymal transition (metastasis)
How do tumour cells differ to embryonic cells?
- Tumour cells escape normal controls
- Proliferation
- Differentiation
- Growth
Where do most cancers occur and what does this contain?
In epithelial - contain stem cells which continue to proliferate
What is cancer caused by overactivation of Hh signalling called?
How can this be treated?
Medulloblastoma: caused by mutation in Ptch 1 (tumour supressor)
- Smo active even in absence of Hh
- GDC-449: blocks Smo activity (like cyclopamine)
- Second mutation in one tumour cell causes drug resistance so cyclopamine can’t bind
- Smo can continue to activate Gli (treatment doesnt last long)
Is Ptc a tumour supressor or oncogene?
Tumour supressor
Is Smo a tumour supressor or oncogene?
Oncogene
How can we make new pancreatic beta cells from stem cells?
- Making a stem cell: best to take cells from patients to turn into stem cells before beta cells
- Make into endoderm: differentiation factors FoxA2, Pdx1 - put through protocol with growth factors
- Differentiate back to beta cells
- Check cell function: check cells can release insulin in response to lgucose
- Introduce cells back into patient
What is totipotent?
Cells with potential to form everything
What is pluripotent?
Cell that can form any cell type within embryo
Can gene expression in nuclei from differentiated cells be changed?
Yes under special circumstances
Can gene expression be controlled by cytoplasmic factors?
Yes
How was nuclear transfer from adult skin cells used to test nuclear potency?
Conclusions?
Skin cells taken from webbing of Xenopus foot
Looked at keratin expression
Trafer nuclei to irradiated, unfertilised egg
Initially doesn’t develop
Carry out serial nuclear transfer
Clones of tadpoles formed
Conclusion: Nuclei of differentiated cells can be reprogrammed to become pluripotent
What are the exceptions to rule that the genome remains constant during development?
- Chromosome loss in Parascaris (a complete chromosome set is retained only in the germ cells)
- Immunoglobulin gene rearrangements in differentiated B lymphocytes
(generating diversity at the DNA level in genes coding for antibody molecules)
Are genes lost or retained during cell differentiation?
Retained
What is the experimental evidence to show that genes are not lost in differentiation, and that nuclei retain potency?
- Lens regeneration in the newt
- Activation of gene expression in heterokaryons
- Activation of gene expression following nuclear transfer in oocytes
- Genomic sequencing
What is the experimental evidence to show that a somatic nucleus contains all genetic information to direct cell differentiation?
- Nuclear transfer exp. in frogs
2. Nuclear transfer in mammals (Dolly)
What are proneural clusters?
Groups of cells in neurectoderm
- Beginning to differentiate apart from neural cells
- One cell becomes neuroblast and others become epidermis
What is the position of proneural clusters determined by?
AP and DV genes
Normally bicoid and toll