Lecture 17. Cell Signalling in Development Flashcards

(86 cards)

1
Q

What is induction ?

A

Where one group of cells influences the development of a neighbouring group of cells

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2
Q

Who was induction first demonstrated by ?

A

Hans Spermann and Hilde Mangold

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3
Q

What is the important conclusion of the organiser experiment ?

A

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

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4
Q

How can induction be achieved at the molecular level ?

A

By cells sending molecular signals to neighboring cells

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5
Q

What type of cell signaling is used to achieve induction at molecular level ?

A

Paracrine signalling

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6
Q

What is signal transduction ?

A

The mechanism that relays the signal received at the cell surface to the nucleus

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7
Q

What is the ultimate effect of cell signaling at the cell surface ?

A

A change in gene expression in the nucleus

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8
Q

What do cells need on their cell surfaces to respond in a particular way ?

A

A particular receptor

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9
Q

What happens as a result of only cells that possess a particular receptor on their surface can respond in a particular way ?

A
  1. Some cells will not respond at all to a signal if they dont have a receptor
  2. Two different cells can respond in different ways to the same signal (if they possess different receptors)
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10
Q

What is competence ?

A

The ability to respond to a signal

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11
Q

What is the ligand or signal of the TGF-beta pathway ?

A

BMP2

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12
Q

What is the receptors of the TGF-beta pathway ?

A

Tgfbr1

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13
Q

What is the transcription factor of the TGF-beta pathway ?

A

Smad

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14
Q

What are the roles in development in TGF-beta pathway ?

A
  1. Roles at all stages

2. Mesoderm induction

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15
Q

What is the signal in the Wnt signalling pathway ?

A

Wnt1

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16
Q

What is the receptor in the Wnt pathway ?

A

Frizzled/ B-catenin

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17
Q

What is the transcription factor in the Wnt signaling pathway ?

A

Tcf/Lef

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18
Q

What is some of the roles in the development of the Wnt pathway ?

A
  1. Roles at all stages
  2. Positional information at all regions
  3. Limb development
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19
Q

What is the signal in the Delta-notch pathway ?

A

Delta-like

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20
Q

What is the receptor in the delta-notch pathway ?

A

Notch

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21
Q

What is the transcription factor in the delta-notch pathway ?

A

Cst

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22
Q

What are the roles in development in the delta-notch pathway ?

A
  1. Roles at all stages
  2. Left-right asymmetry
  3. Neurogenesis
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23
Q

What is the signal in the Hedgehog signaling pathway ?

A

Sonic hedgehog

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24
Q

What is the receptor in the hedgehog pathway ?

A

Patched/smoothened

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25
What is the transcription factor in the hedgehog pathway ?
Gli
26
What is the role in development in the hedgehog signaling pathway ?
1. Positional information - neural tube and limb
27
What is the signal in the FGF pathway ?
FGF8
28
What is the receptor in the FGF pathway ?
Fgfr
29
What is the transcription factor in the FGF pathway ?
Not known
30
What are the roles in FGF pathway ?
1. Roles at all stages 2. AER of limb bud 3. Gastrulation - maintaining mesoderm
31
What is the signal in the Hippo pathway ?
Stress
32
What is the receptor in the hippo pathway ?
Fat4 eg yap/taz
33
What is the transcription factor in the hippo pathway ?
Tead4
34
What is the roles of hippo in development ?
1. Early mammalian | 2. Kidney/skeletal
35
Induction in the C. elegans: What does the vulva develop from ?
Six cells present on the ventral surface of the second stage larva
36
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
37
What is the signaling pathway involved in the C. Elegans ?
EGF pathway
38
What is the function of hedgehog ?
Definition of segments
39
Where was the hedgehog gene first identified ?
In drosphilia mutant screens
40
What is the ventral surface of the hedgehog gene covered in ?
Denticles
41
How many homologues does the vertebrate of drosphilia hedgehog have ?
3
42
What are the 3 homologues of drosphilia hedgehog ?
1. Ihh - Indian hedgehog 2. Dhh - desert hedgehog 3. Shh - sonic hedgehog
43
Where is hedgehog expressed ?
Restricted domains
44
What maintains the segment boundary in hedgehog ?
Interactions between hedgehog and wingless
45
What is the role of Ihh in gene expression in mouse embryo ?
In bone formation
46
What is the role of Shh in gene expression in mice ?
neural tubes developing limb buds
47
What is the role of Dhh in gene expression in mouse embryo ?
Male reproductive system - testes development
48
Where is the zone of polarising activity located ?
In the posterior mesoderm
49
What is the zone of polarising activity defined by ?
Its activity when transplanted to another region
50
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
51
What was used to show where Shh is expressed ?
In situ hybridisation
52
What is the zone of polarising activity molecularly defined by ?
Sonic hedgehog gene expression
53
What does transplanting cells that express sonic hedgehog to the anterior limb mimick ?
zone of polarising activity transplantation
54
What is the sonic hedgehog a major active component of ?
Zone of polarising activity
55
What is sonic hedgehog required for ?
Pattern formation of the limb along the anterior posterior axis
56
What are mutations in the sonic hedgehog responsible for ?
Human limb malformations such as human preaxial polydactyl
57
What does the removal of the sonic hedgehog gene expression in the developing mouse limb lead to ?
Truncation of the distal structure
58
What does the removal of the AER at different stages lead to ?
Truncation of the limb at different points along the p/d axis
59
Where is AER a major signalling centre of ?
Limb
60
What does AER secrete ?
FGFR
61
What happens if AER is removed but beads containing FGF8 are added ?
Limb development can continue near to normal
62
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
63
What is the function of wingless ?
Works with hedgehog to establish segment boundaries
64
Where is wingless expressed ?
Restricted domains
65
In mice and humans how many wnt genes are there ?
19
66
What are wnt proteins critical for in mice and humans ?
1. Patterning somites | 2. Development of nervous and muscle systems
67
What does Wnt bind do ?
The frizzled receptor
68
How many frizzled receptors in mice ?
10
69
What is the roles of development in the wnt signalling in mice ?
1. Patterning of cells 2. Regulating cell proliferation 3. Patterning of limbs 4. Urogenital system development 5. Stem cell control
70
What are the series of events that cells are given instructions on how to behave ?
1. when to divide 2. when to migrate 3. when to invade
71
What sort of disease in cancer ?
Progressive
72
What type of growth occurs in cancer ?
Growth control loss
73
What type of localised growth occurs in cancer ?
Benign
74
What does benign localised growth in cancer result in ?
Metastasis and malignancy
75
What are some environmental conditions that cause mutations in genes that can cause cancer ?
1. UV irradiation 2. Cigarette smoke 3. Certain viruses 4. High dietary fat
76
What are the two categories of genes that when mutated can lead to cancer ?
1. Proto-oncogenes | 2. Tumour suppressors
77
What are proto-oncogenes and tumour supressors function ?
Regulators of cellular behavior
78
What is a common cause of colon cancer ?
Wnt and cancer pathway malfunction
79
What is the function of wnt genes in the gut ?
Needed for development and regulation of stem cell population for repair of gut lining
80
What is the function of the gene product APC ?
Involved in controlling how a wnt signal is interpretated inside a receiving cell
81
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
82
What does APC help to do ?
Keep the wnt pathway off in the absence of wnt signalling
83
By studying embyronic development what can we find out ?
1. How cell controls are established in normal cells 2. How events such as cell division, migration and invasion are controlled in the embryo 3. How programmed cell death is controlled in the embryo 4. How a blood supply is established to nourish developing organs
84
What is a possible treatment for cancer ?
If the Shh pathway is blocked the tumor regresses
85
What is tumorigenesis ?
Sporadic mutations or other mechanisms
86
What is hedgehog involved in cancer ?
Evidence for re-activation of the pathways in tumorigenesis