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BMS 242 - Principles of Developmental Biology > Branching morphogenesis in organs > Flashcards

Branching morphogenesis in organs Flashcards

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1
Q

What organs is branching morphogenesis required in?

Examples?

A

Organs where a high surface area:volume ratio is needed

Lung
Uteretic bud (gives rise to the kidney)
Prostate
Mammary gland 
Pancreas
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2
Q

What structure is formed in through branching morphogenesis?

A

Tree-like structure with a large surface area

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3
Q

What is the structure of the kidneys?

A

1000s of repeating units made of:

  • Nephron
  • Collecting duct
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4
Q

What is the collecting duct attached to in the kidneys?

A

At one end:
- Feeds into the nephron

At the other end:
- Connected to blood supply

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5
Q

In the kidney, what is the equivalent of the ‘twigs’ of the tree?

‘trunk’ of the tree?

A

Twigs - Collecting ducts

Trunk - Ureter

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6
Q

What is the DEFINATIVE kidney called?

A

The METANEPHROS

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7
Q

Where is the metanephros developed from?

A

The INTERMEDIATE mesoderm

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8
Q

What forms at the very posterior of each of the lines of intermediate mesoderm?

A

2 bud structures (one each side)

Called the URETERIC BUDS

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9
Q

Where are the ureteric buds formed from?

What type of cells are they made up from?

A

Formed from the intermediate mesoderm

Made up up epithelial-like cells

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10
Q

Where does the ureteric bud poke out into?

A

Into adjacent mesenchymal cells called the metanephric mesenchyme

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11
Q

What does the definitive kidney (metanephros) arise from?

A

From a result of RECIPROCAL INDUCTIVE interactions between the:

  • Ureteric bud
  • Metanephric mesenchyme
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12
Q

What is the metanephric mesenchyme sometimes known as?

A

The metanephric blastema

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13
Q

What are reciprocal inductive interactions?

A

1) One tissue signals to the 2nd tissue - causing the 2nd tissue to change
2) This newly changes tissue can now signal back to the 1st tissue and cause it to change
3) Happens repeatedly to build the kidney

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14
Q

Which structure of the developing kidney undergoes branching morphogenesis?

How?

A

The ureteric bud

Receives signals from the metanephric mesenchyme

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15
Q

What are the steps of branching morphogenesis of the ureteric bud?

A

1) GDNF signals from the MM cause PROLIFERATION and OUTGROWTH of the ‘tip cells’
2) Ureteric bud ‘bulges’

3) Cells in the middle to the tip of the ureteric bud see MORE of the signal
HOWEVER, this causes these leading-edge tip cells to ARREST proliferation - causing the tip of the bud to flatten

4) Lateral tip cells continue to proliferate - resulting in the formation of a cleft, with 2 tips (a branch)
5) Lateral tips are still surrounded by the mesenchyme - process repeats

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16
Q

What receptors do the cells of the ureteric bud have?

What is it called?

What type of receptor is it?

A

GDNF receptors

Called Ret

A receptor tyrosine kinase

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17
Q

What happens when GDNF binds to Ret in one the bud cells?

A
  • Signalling transduction pathway
  • Up regulation of core TRANSCRIPTION FACTORS
  • Up regulation of more signalling pathways
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18
Q

Why does the ureteric bud begin to bulge?

A

Ureteric bud cells in the tip proliferate in response to GDNF but cannot move as they are EPITHELIAL

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19
Q

What do the new signals in the epithelial cells of the ureteric bud act on?

A

Some signals act back onto the mesenchyme

BUT some signals act back onto the epithelial cells:

  • To help regulate gene expression profiles and govern the response of the cell
  • To help lead to bifurication
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20
Q

What responses of the epithelial cells help lead to bifurication?

A
  • Local proliferation
  • Orientated cell division
  • Cell migration
  • Cell adhesion
  • Cell shape
  • ECM remodelling
21
Q

What happens are the same time as the metanephric duct signalling to the ureteric bud, causing it to branch?

What does this cause?

A

The ureteric bud signals to LOCAL parts of the metanephric mesenchyme

Causing the cells to CONDENSE and undergo a MTE transition, to form RENAL EPITHELIUM and then RENAL VESICLES

22
Q

What do renal vesicles form?

How?

A

Form nephrons

How:

  • Grows into a comma-shaped body
  • Becomes S shapes body
  • Gets longer and longer
  • At one end - fuses with the collecting duct
  • At the other end - attracts endothelial capillaries (to form the Bowmann’s capsule)
  • Ultimately, will get the complete nephron (at the S-shaped structure grows - it bends to form the loop of henle
23
Q

Where is the collecting duct that the S shaped renal vesicle fuses with?

A

The tip of the ureteric bud

24
Q

How does the distal end of the renal vesicle fuse with the ureteric bud?

A

By selective apoptosis

25
Q

How is the proximal end of the renal vesicle polarised?

A

Provides local signals for angiogenesis - so that capillaries form

26
Q

How many renal vesicles fuse in each kidney?

A

10^6

27
Q

How can we study the process of branching morphogensis in the kidney in ‘real time’

A

Using transgenic animals:

  • Clone promoter (that normally drives a gene expressed in the ureteric bud) UPSTREAM of GFP
  • Ureteric bud that forms then glows green
28
Q

Where did the understanding of branching morphogenesis in the lungs come from?

A

Through analysis of drosophila tracheal development

29
Q

If branching of the trachea a conserved process?

A

Yes

30
Q

What 2 tissues do the lungs develop from?

A

The mesoderm and endoderm

31
Q

What parts of the lungs do the endoderm give rise to?

How?

A

Epithelial lining of the trachea, larynx, bronchi, alveoli

Through branching morphogenesis

32
Q

Where is the mesoderm of the lungs present?

What does it give rise to?

A

Present around the tips of the developing buds

Give rise to:

  • Cartilage
  • Muscle
  • Connective tissue
33
Q

What structure do the trachea, bronchi, bronchioles etc. develop from?

What is this?

A

From the RESPIRATORY DIVERTICULUM

An ENDODERM bud that grows out from the ESOPHAGUS

34
Q

What happens to the tip of the respiratory diverticulum?

What does this form?

A

Undergoes branching morphogenesis - first branches go left and right

Forms the lung buds

35
Q

When do the lung buds form in humans?

A

About the 4th week

36
Q

What cells is the respiratory diverticulum made from?

A

Endothelial epithelial cells

37
Q

What is outgrowth of the respiratory diverticulum dependant on?

What do these signals do?

A
  • Signals from the adjacent mesoderm/mesenchyme
  • Which act on the receptors in the respiratory diverticulum and tell the cells to proliferate
  • Causing the tube to get longer
38
Q

What always surrounds the lungs/respiratory diverticulum?

A

Sac of mesoderm

39
Q

In the lungs, what do the mesenchymal cells express?

A

FGF10

40
Q

In the lungs, what does the respiratory diverticulum express?

A

FGF receptor

41
Q

What is the process of branching morphogenesis in the lungs?

A

1) Endothelial epithelial cells (express FGFR) respond to the secretion of FGF from the nearby mesenchyme by PROLIFERATING
- Causes bud formation and extension towards the FGF source
2) Cells are the leading tip see the highest concentration of FGF

  • Causing the expression of secondary genes in the tip
  • Turning the leading tip into a signalling centre

3) BMP4 expressed at the highest levels in the ‘leading edge’ tip cells

  • Autonomously inhibits epithelial cell proliferation
  • Causing flattening of the of the bud

4) At the same time, shh expressed by the leading tip cells diffuses into the mesenchyme and INHIBITS FGF10 expression in the mesenchyme closest to the tip
- This SPLITS FGF10 expression - so that is surrounds the tips and promotes the next round of branching

42
Q

What are the secondary genes that are expressed in the leading tip as a result of seeing the highest concentration of FGFs?

A

BMP4

Shh

43
Q

What does ‘Sprouty’ do?

Why?

A

Limits the action of Fgf10

So the branching is RESTRICTED to the TIP of the branch

44
Q

What is the expression of Sprouty induced by?

A

FGF10 over a long time period (after it has induced shh and BMP4 signalling)

45
Q

What type of feedback loop is between Fgf10 and sprouty?

A

Negative feedback

Fgf10 induces its own inhibitor - to limit its time of action

46
Q

What else occurs during branching in the lung?

Why?

A

Recruitment of blood capillaries

For gas exchange

47
Q

What fraction of the adult alveoli are present at birth?

What does this show?

A

1/6

Shows that respiratory bronchioles and alveoli continue to increase in number after birth

48
Q

Where are the ureteric bud and the metenephric mesenchyme derived from?

A

The intermediate mesoderm

49
Q

What does shh released from the leading tip cells do?

A
  • Inhibits FGF10 expression at in the mesoderm/mesenchyme closest to the tip
  • Splitting Fgf10 expression - promoting next round of branching

BMS 242 - Principles of Developmental Biology (15 decks)

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