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Developmental Biology > L16 - Branching Morphogenesis in Organs > Flashcards

L16 - Branching Morphogenesis in Organs Flashcards

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1
Q

What organs is branching morphogenesis fundamental in?

A

Fundamental to function in many tissues where high surface area for exchange is required

  • Lung – gas exchange
  • Ureteric bud – gives rise to kidneys
  • Salivary gland
  • Prostate
  • Mammary gland
  • Pancreas
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2
Q

What is the overall kidney structure?

A

Composed of 1000s of repeating units made up of a nephron and collecting duct
- Collecting duct – feeds into the nephron
- Nephron – proximal and distal loops
- 1 end connects to collecting duct
- 1 end connects to the blood
The collecting ducts act as the branches of the tree which all drain into the ureter

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3
Q

The kidney rises as a result of what interaction?

A

Reciprocal inductive interactions between

  • The small outpocketing of an intermediate mesodermal structure - ureteric bud (epithelial)
  • The adjacent mesenchyme - metanephric mesenchyme
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4
Q

What is metanephros?

A

The formation of definitive kidney

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5
Q

The branching morphogenesis of the ureteric bud is governed by signals from?

A

The metanephric mesenchyme

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6
Q

Branching morphogenesis of the ureteric bud method

A
  1. Signal from mesenchyme causes proliferation and outgrowth of bud tip cells
    - GDNF signal binds to RET receptor tyrosine kinase on bud tip cells
  2. Signal transduction pathway activated
    - Causes proliferation, migration and outgrowth
  3. Central leading-edge tip cell arrests its proliferation, resulting in a flattening of the bud
    - See the highest concentration of GDNF
  4. Lateral tip cells continue to proliferate, resulting in formation of cleft and two tips - branches
    - See lower concentrations of GDNF
  5. Lateral tip cells still surrounded by mesenchyme so process repeats
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7
Q

Where do the two signals involved in branching morphogenesis in the ureteric bud come from?

A

First signals come from a mesenchyme tissue

Then signals from within the epithelial ureteric bud act locally to govern gene expression

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8
Q

Signals coming from the epithelial ureteric bud lead to changes in what?

A

Lead to change in transcription factor gene expression that autonomously lead to changes in

  • Cell migration
  • Cell proliferation
  • Cell adhesion
  • Cell shape
  • ECM remodelling
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9
Q

The repeated process in the ureteric bud results in the formation of multiple branches that form?

A

Go on to differentiate into multiple collecting ducts of each kidney

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10
Q

At the same time collecting ducts are forming what else is formed via reciprocal induction interaction?

A

Ureteric bud signals to local parts of metanephric mesenchyme
Induces them to form definitive nephric tubules
Induces local nephrogenic mesenchyme to condense around the bud
- Undergo mesenchymal-to-epithelial cell transition
- Form renal epithelium and then renal vesicles

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11
Q

How was renal vesicles formed?

A

Formed by transcription factors induced in renal epithelium that cause cell-shape changes

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12
Q

What does a renal vesicle go on to form?

A

A nephron

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13
Q

What shape is a renal vesicle?

A

S-shaped body which is polarised

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14
Q

What does the proximal end of the renal vesicle do?

A

Fuse with the bud

Provide local signals for angiogenesis – so capillaries form

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15
Q

What does the distal end of the renal vesicle do?

A

Attract endothelial capillaries

Fuses with collecting duct by selective apoptosis

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16
Q

How do we study changes in the ureteric bud in real time?

A

Use transgenic animals, organ cultures and sophisticated imaging
Cloned promoter that normally drives a gene only expressed in the ureteric bud upstream of GFP
- Transgenic animal then contains a ureteric bud that expresses GFP
- Allows studying of branching

17
Q

What do kidneys form from?

A

Kidneys form from a mesodermal line of cells - intermediate mesoderm
- Cells extend along the whole of the posterior body

18
Q

How were the molecular mechanisms of lung morphogenesis discovered?

A

Through analysis of Drosophila tracheal development
Conserved molecular mechanism for the breathing apparatus
The role of FGF10 and its inhibitor Sprouty

19
Q

What two tissues are lungs derived from?

A

Endoderm

Mesoderm

20
Q

What does lung endoderm give rise to?

A

Will give rise to epithelial lining of trachea, larynx, bronchi, alveoli
Occurs through branching morphogenesis

21
Q

What does lung mesoderm give rise to?

A

Will gives rise to cartilage, muscle and connective tissue

22
Q

Where do the trachea, bronchi, bronchioles and alveoli come from?

A

All arise from a bud - respiratory diverticulum

Tip of the respiratory diverticulum then begins to undergo branching morphogenesis

23
Q

In humans the lung buds form during which week?

A

4th week

24
Q

How does the respiratory diverticulum divide?

A

Respiratory diverticulum is composed of endothelial epithelial cells
Its outgrowth is dependent on signals from adjacent mesoderm/mesenchyme
Lung buds then undergo further branching
A sac of mesoderm surrounds each lung bud

25
Q

Why is branching limited to the tips in the lungs method

A
  1. Endothelial epithelial cells respond to the secretion of FGF from nearby mesenchyme
  2. Respond by bud formation and extension towards FGF source
  3. Exposure of tip cells to high FGF concentrations induces expression of secondary genes in the tip
    o Including genes that code for – BMP4, Shh and Sprouty 2
    o Turning tips of bronchial branches into signaling centers
  4. BMP4 is expressed at highest levels in leading edge tip cells
  5. It autonomously inhibits epithelial cell proliferation limiting branch extension - flattening the bud
  6. At the same time, Shh expressed by tip cells diffuses to the mesenchyme
  7. It inhibits FGF10 expression in the mesenchyme nearest the tip
  8. This splits FGF10 expression promoting the next round of branching
  9. Sprouty limits the action of Fgf10 so that branching is restricted to the tip of the branch
26
Q

How does sprout act through a negative feedback loop?

A

FGF10 induces expression of genes that direct growth and proliferation
Over a longer time FGF induces expression Sprouty
- Sprouty inhibits FGF signalling
A signal induces its own inhibitor, to limit the time of its own action

27
Q

What increases in size and number after birth?

A

Respiratory bronchioles and alveoli continue to increase in number after birth
Only 1/6 of adult alveoli are present at birth

Developmental Biology (16 decks)

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