L16 - Branching Morphogenesis Flashcards

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1
Q

What is branching morphogenesis essential to

A

The function of tissues which require a high surface area for exchange

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2
Q

Give examples of where branching morphgenesis occurs

A
Lung 
Ureteric bud 
Salivary gland 
Prostate 
Mammary gland 
Pancreas
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3
Q

Branching morphogenesis is essentially to process by which _____________ are created

A

Tree-like // branched structures

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4
Q

What are the repeating units of the kindey

A

Nephron

Collecting duct

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5
Q

Formation of the kidney arises through

A

Reciprocal inductive interactions between the ureteric bud and the metanephric mesenchyme

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6
Q

What is recirpocal induction

A

Cell 1 signals causing cell 2 to change

Cell 2 then signals causing a change in cell 1

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7
Q

what is the ureteric bud

A

Outpocketing of intermediate mesoderm

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8
Q

What is the metanephric mesenchyme

A

Mesenchyme which is adjacent to the uretric bud

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9
Q

Describe the recpeirocal inductive eventss with the ureteric bud and the metanephric mesenchyme

A

Either side of the midline - parallel lines of intermeidate mesoderm
At very posterior bud like stuctures form - ureteric bud
ureteric bud pokes into mesodermal cells - metanephric mesenchyme
Interaction repeats throughout development

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10
Q

What are the (4) key steps in branching morphogenesis of the ureteric bud

A

Signals from the metanephric mesenchyme cause proliferation and outgrowth of bud tip cells

Leading edge tip cell arrests its proliferation resulting in the flattening of the bud

Lateral tip cells contunue proliferating –> formation of a cleft and two tips

Lateral tip cell still surrounded by mesencehyme and the process repeats

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11
Q

What is the signal from the metanephric mesenchyme - what is its receptor

A

GDNF

Ret

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12
Q

What type of receptor is Ret

A

RTK

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13
Q

Why do leading edge tip cells arrest their proliferation

A

See very high levels of GDNF and this has the effect of inhibiting proliferation

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14
Q

Why are lateral tip cells still able to proliferate>?

A

Since they only see intermediate levels of GDNF signalling

This has the effect of causing cell proliferation

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15
Q

GDNF from the

Acting on RET receptors of the

A

Metanephric mesenchyme

Ureteric bud

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16
Q

What is the effect of signals from the metanephric mesenchyme (what do they cause in order to get reshaping)

A

Activate signalling pathways
Changes in gene expression
Cellular response

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17
Q

What cellular responses are involved with the bifuraction of the ureteric bud

A
Local proliferation 
Oriented division 
Cell migration
Cell adhesion 
Shape
ECM remodelling
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18
Q

Describe what is meant by bifurcation of the ureteric bud being an itterative process

A

It is a repeated process which will form many branches

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19
Q

The many branches formed from the ureteric bud will form

A

The mutliple collecting ducts of the kidney

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20
Q

What happens at the same time as the uteric bud is bifucating

A

The uteric bud signals to the local parts of metanephric mesechyme inducing them to form definitive nephric tubules

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21
Q

Describe what type of change the uretric bud causes to the metanephric mesenchyme

A

Causes it to undergo a mesenchymal to epithelial transition

22
Q

When the metanephric mesenchyme undergoes a M –> E transition what is formed - what is the next strucuture formed from this process

A

Renal epithliumm and then the renal vesicles

23
Q

Describe the stages of renal vesicle proliferation to form a nephron

A

Proliferation forms an S shaped body
One end of S shaped body fuses with the collecting duct
Other end of the S shaped body attracts blood vessels and leads to the formation of the glomerulus

24
Q

What happens to the DISTAl end of the S shaped body

A

Fuses with the uretric bud - collecting duct

25
Q

The ureteric bud undergoes ________

A

Repeated branching morphogenesis

26
Q

How many renal vesicle inducing buds in each kidney

A

10 million

27
Q

Describe a method of studying renal development in real time

A

Clone promoter of a gene being expressed in the ureteric bud
Express GFP under that promoter
GFP expression can be seen in cells of the ureteric bud

28
Q

Branching in the lung controlled by

A

FGF10 and sprout-2

29
Q

Describe where our understanding of lung development came from -

A

Drosophila
Tracheal development in the dropsohila - molecular mechanisms used for the development of breathing apparatus are highly conserved ``

30
Q

what two tissues in the lung derived from

A

Endoderm and mesoderm

31
Q

Endoderm forms what lung strucutures

A

Epithelilal lining of the trachea
Larynx
Bronchi
Alveoli

32
Q

Mesoderm forms what lung strucutres

A

Cartilage
Muscle
Connective tissue

33
Q

Trachea, bronchi, bronchioles and alveoli all arise from the

A

Respiratory diverticulum

34
Q

What does the respiratory diverticulum grow out off

A

Trachea

35
Q

Outgrowth of the respiratory diverticulum is dependent on

A

Signals from the adjacent mesoderm/mesnechyme

36
Q

What surrounds each lung bud

A

Sac of mesoderm

37
Q

What is the medial edge of the sac of mesoderm lining the lungs

A

Visceral pleura

38
Q

What is the outer edge of the sac of mesoderm lining the lungs

A

Parietal pleura

39
Q

Endothelilal cells expres ____________ that means they are able to respond to ________ from the surrounding mesenchyme

A

FGFR

FGF10 - from the surrounding mesenchyme

40
Q

Describe the effect of exposing the tip cells to high concentrations of FGF10

A

Induces the expression of secondary genes in the tip

41
Q

What seocndary genes are expressed in the tip in response to FGF10

A

BMP4
Shh
Sprouty

42
Q

Expression of the seocnary genes turns the tips into

A

Signalling ccentres

43
Q

Describe where BMP4 expression is highest

What is the effect that this has here

A

In the leading edge tip cells

Inhibits epitehial cell proliferation - causes flattening

44
Q

What is the effect of Shh in the lung tip

A

Diffuses to the mesenchyme and inhibits expression of FGF10 nearing to the tip

This splits FGF10 expression nearest the tip

45
Q

What is the effect of Sprout-2

A

Limits the action of FGF10

Means that branching is restricted to the very tip

46
Q

Describe the neative feedback loop of FGF10 and sprouty

A

Over a slightly longer timefram FGF10 induces expression of sprouty
Sprouty inhibts FGF signalling

47
Q

What are the three periods in the development of lung tissue

A

Canalicular period
Terminal sac period
Alveolar period

48
Q

What happens in the terminal sac period

A

Formation of type 1 sqamous cells (pneumocytes_

49
Q

What happens in the alveolar sac period

A

production of type 2 squamous cells involved in the production of surfactant

50
Q

How is the extensive capillary network required for gas exchange created

A

Alveoli generated which attracts endothelial blood cells