Lecture 17. Cell Signalling in Development Flashcards
What is induction ?
Where one group of cells influences the development of a neighbouring group of cells
Who was induction first demonstrated by ?
Hans Spermann and Hilde Mangold
What is the important conclusion of the organiser experiment ?
Organiser cells from the donor could change the fate of the recipient cells and can set in motion a chain of events leading to the production of a new body plan
How can induction be achieved at the molecular level ?
By cells sending molecular signals to neighboring cells
What type of cell signaling is used to achieve induction at molecular level ?
Paracrine signalling
What is signal transduction ?
The mechanism that relays the signal received at the cell surface to the nucleus
What is the ultimate effect of cell signaling at the cell surface ?
A change in gene expression in the nucleus
What do cells need on their cell surfaces to respond in a particular way ?
A particular receptor
What happens as a result of only cells that possess a particular receptor on their surface can respond in a particular way ?
- Some cells will not respond at all to a signal if they dont have a receptor
- Two different cells can respond in different ways to the same signal (if they possess different receptors)
What is competence ?
The ability to respond to a signal
What is the ligand or signal of the TGF-beta pathway ?
BMP2
What is the receptors of the TGF-beta pathway ?
Tgfbr1
What is the transcription factor of the TGF-beta pathway ?
Smad
What are the roles in development in TGF-beta pathway ?
- Roles at all stages
2. Mesoderm induction
What is the signal in the Wnt signalling pathway ?
Wnt1
What is the receptor in the Wnt pathway ?
Frizzled/ B-catenin
What is the transcription factor in the Wnt signaling pathway ?
Tcf/Lef
What is some of the roles in the development of the Wnt pathway ?
- Roles at all stages
- Positional information at all regions
- Limb development
What is the signal in the Delta-notch pathway ?
Delta-like
What is the receptor in the delta-notch pathway ?
Notch
What is the transcription factor in the delta-notch pathway ?
Cst
What are the roles in development in the delta-notch pathway ?
- Roles at all stages
- Left-right asymmetry
- Neurogenesis
What is the signal in the Hedgehog signaling pathway ?
Sonic hedgehog
What is the receptor in the hedgehog pathway ?
Patched/smoothened
What is the transcription factor in the hedgehog pathway ?
Gli
What is the role in development in the hedgehog signaling pathway ?
- Positional information - neural tube and limb
What is the signal in the FGF pathway ?
FGF8
What is the receptor in the FGF pathway ?
Fgfr
What is the transcription factor in the FGF pathway ?
Not known
What are the roles in FGF pathway ?
- Roles at all stages
- AER of limb bud
- Gastrulation - maintaining mesoderm
What is the signal in the Hippo pathway ?
Stress
What is the receptor in the hippo pathway ?
Fat4 eg yap/taz
What is the transcription factor in the hippo pathway ?
Tead4
What is the roles of hippo in development ?
- Early mammalian
2. Kidney/skeletal
Induction in the C. elegans: What does the vulva develop from ?
Six cells present on the ventral surface of the second stage larva
Induction in the C. Elegans: What initiates a cascade of signals that establishes the fate of the precursor cells ?
A single cell in the embryonic gonad, called the anchor cell
What is the signaling pathway involved in the C. Elegans ?
EGF pathway
What is the function of hedgehog ?
Definition of segments
Where was the hedgehog gene first identified ?
In drosphilia mutant screens
What is the ventral surface of the hedgehog gene covered in ?
Denticles
How many homologues does the vertebrate of drosphilia hedgehog have ?
3
What are the 3 homologues of drosphilia hedgehog ?
- Ihh - Indian hedgehog
- Dhh - desert hedgehog
- Shh - sonic hedgehog
Where is hedgehog expressed ?
Restricted domains
What maintains the segment boundary in hedgehog ?
Interactions between hedgehog and wingless
What is the role of Ihh in gene expression in mouse embryo ?
In bone formation
What is the role of Shh in gene expression in mice ?
neural tubes developing limb buds
What is the role of Dhh in gene expression in mouse embryo ?
Male reproductive system - testes development
Where is the zone of polarising activity located ?
In the posterior mesoderm
What is the zone of polarising activity defined by ?
Its activity when transplanted to another region
What happens to the zone of polarising activity when transplanted to the anterior ?
It induces a duplication of the A/PP pattern of digits that will form
What was used to show where Shh is expressed ?
In situ hybridisation
What is the zone of polarising activity molecularly defined by ?
Sonic hedgehog gene expression
What does transplanting cells that express sonic hedgehog to the anterior limb mimick ?
zone of polarising activity transplantation
What is the sonic hedgehog a major active component of ?
Zone of polarising activity
What is sonic hedgehog required for ?
Pattern formation of the limb along the anterior posterior axis
What are mutations in the sonic hedgehog responsible for ?
Human limb malformations such as human preaxial polydactyl
What does the removal of the sonic hedgehog gene expression in the developing mouse limb lead to ?
Truncation of the distal structure
What does the removal of the AER at different stages lead to ?
Truncation of the limb at different points along the p/d axis
Where is AER a major signalling centre of ?
Limb
What does AER secrete ?
FGFR
What happens if AER is removed but beads containing FGF8 are added ?
Limb development can continue near to normal
What is FGF8 expression in AER necessary for ?
The outgrowth of the limb and for the patterning of the limb along the proximal/distal axid
What is the function of wingless ?
Works with hedgehog to establish segment boundaries
Where is wingless expressed ?
Restricted domains
In mice and humans how many wnt genes are there ?
19
What are wnt proteins critical for in mice and humans ?
- Patterning somites
2. Development of nervous and muscle systems
What does Wnt bind do ?
The frizzled receptor
How many frizzled receptors in mice ?
10
What is the roles of development in the wnt signalling in mice ?
- Patterning of cells
- Regulating cell proliferation
- Patterning of limbs
- Urogenital system development
- Stem cell control
What are the series of events that cells are given instructions on how to behave ?
- when to divide
- when to migrate
- when to invade
What sort of disease in cancer ?
Progressive
What type of growth occurs in cancer ?
Growth control loss
What type of localised growth occurs in cancer ?
Benign
What does benign localised growth in cancer result in ?
Metastasis and malignancy
What are some environmental conditions that cause mutations in genes that can cause cancer ?
- UV irradiation
- Cigarette smoke
- Certain viruses
- High dietary fat
What are the two categories of genes that when mutated can lead to cancer ?
- Proto-oncogenes
2. Tumour suppressors
What are proto-oncogenes and tumour supressors function ?
Regulators of cellular behavior
What is a common cause of colon cancer ?
Wnt and cancer pathway malfunction
What is the function of wnt genes in the gut ?
Needed for development and regulation of stem cell population for repair of gut lining
What is the function of the gene product APC ?
Involved in controlling how a wnt signal is interpretated inside a receiving cell
What can stem cells in the adult gut be stimulated to do ?
To divide and produce more gut lining cells by the wnt cell signalling molecule
What does APC help to do ?
Keep the wnt pathway off in the absence of wnt signalling
By studying embyronic development what can we find out ?
- How cell controls are established in normal cells
- How events such as cell division, migration and invasion are controlled in the embryo
- How programmed cell death is controlled in the embryo
- How a blood supply is established to nourish developing organs
What is a possible treatment for cancer ?
If the Shh pathway is blocked the tumor regresses
What is tumorigenesis ?
Sporadic mutations or other mechanisms
What is hedgehog involved in cancer ?
Evidence for re-activation of the pathways in tumorigenesis