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Cells To Organisms > Organogenesis > Flashcards

Organogenesis Flashcards

1
Q

What are the basic units of the kidney?

A

Nephron (metanephric mesenchyme) and collecting duct (uteric bud)

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2
Q

What does the paraxial mesoderm give rise to?

A

somites-> skeletal muscle

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3
Q

What does the intermediate mesoderm give rise to?

A

Kidney

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4
Q

What does the lateral plate mesoderm give rise to?

A

circulatory system

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5
Q

What TF control gene expression in kidney differentiation?

A

Pax2/8 (paired box) and Lim-1 (homeodomain), if remove Lim-1 then no kidneys form (master regulator)

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6
Q

What kinds of sigalling are in kidney differentiation? From what tissues?

A
  1. Paraxial to intermediate paracrine signalling (if seperate paraxial and intermediate then genes stay off so they need to be adjacent)
  2. Lateral to intermediate paracrine signalling (at a medium level of BMP2)

BMP2 is a morphogen

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7
Q

What are reciprocal inductive interactions?

A

Two cells capable of changeing each other via signalling (both are inducers and responders of each other) Eg MM and UB

This is why different tissues can contribute to the same organ and grow in a porportionate way

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8
Q

Grobsteins transfilter assay

A
  1. Kidney rudiement disected
  2. MM seperated from UB
  3. cultured seperately or togetheron polycarbonate filter
    Result: shriveled and died if seperate, UB branchinng and nephrons if together
    Meant that UB and MM were influencing each other
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9
Q

How does UB and MM start uteric branching?

A

Signalling tells UB to start growing into the MM, then the UB starts branching. The tip of the UB swells and then splits in 2, and repeats

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10
Q

What signals do the UB and MM use to promote each other?

A

Ret/GDNF signalling. Ret expressed in nephric duct and tips of uteric branches. GDNF expressed in MM.

Ret is the receptor and GDNF is the signal

GDNF = glilal cell line derived neurotrophic factor

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11
Q

What experiments were done to show how Ret/GDNF signaling works?

A

Experiement 1: remove Ret or GDNF via genetic manipulation or pharmological inhibition results in no nephric branching
Experiement 2: add GDNF soaked bead results in extra branching
Experiement 3: low Ret and normal Ret cells combined= the normal Ret made the branching. High Ret and normal combined= high Ret formed branches.
Relative levels of Ret determine branching activity, GDNF is suffiecent to grow branches

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12
Q

What behaviors drive UB branching?

A
  1. differential cell proliferation
  2. cell rearrangement
  3. localised remodelling of the ECM
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13
Q

What is differential cell proliferation?

A

Eg. The tip of the branch divides more than the trunk does, likely theres increased Ret/GDNF in the tips rather than trunk–(soaked GDNF bead resulted in extra proliferation of the tips)

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14
Q

In regards to cell behaviors that drive UB branching

What is cell rearrangement?

A

Eg. cells move bc of Ret signalling, cells with the most Ret will migrate towards the tips of the buds

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15
Q

In regards to cell behaviours that drive UB branching

What is localized remodelling of the ECM?

A

Kidney mesenchyme represses (secretes GDNF) collagen 18 from forming in the tips of the UB.

If you get rid of the mesenchyme and replace with lung mesenchyme which secretes Wnt2 then you get collagen18 forming in the tips

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16
Q

MET

Mesenchymal to epithelial transition

A

The formation of renal vesicles from the MM. Renal vesicles= formation of the nephron

17
Q

What signals are involved in MET?

A
  1. Wnt9b, paracrine (Wnt9b -/- mouse doesnt do MET and no kidneys formed)
  2. Wnt4, autocrine (induced by Wnt9b and secreted from MM. UB recruits MM until Wnt4 reaches a threshold via quorum sensing)
18
Q

Example of quorum sensing in the kidney:

A

Wnt4 expression weak in loose MM, and strong in the aggregate.

19
Q

Characteristics of a MET epithelilal tube

A
  • Single cell, non-stratified layered epithelial tubulum (has a lumen)
  • Has cadheren and occluding junctions
  • ## Apicobasal polarity (diff transport proteins on either side)
20
Q

What axis does the nephron form along and why?

A

The proximo-distal axis. Important because morphogenic signalling sectioned UB into 3 layers at the renal vessicle stage. Patterning is important bc leads to cell differentiation, if goes wrong its bad eg Barter syndrome

renal vescile-> comma shape-> s shaped body-> nephron

21
Q

What is barter syndrome?

A

Excessive loss of NaCl & K bc of a bad ion transporter in thick loop of henle.

22
Q

Delevoping glomerular capillaries

A

Podocyte precursor cells secrete VEGF (chemoattractant) and endothelial cells sit on top of them, eventually develop into glomerulus. Mutant: no VEGF no capillary formation

Vascular endothelial growth factor= VEGF

endothelial cells end up being the glomular capillary. Podocytes are the blood filtration

23
Q

What is chemotaxis?

A

Responding to signals based on their gradient. Chemattractant= towards the source/up the gradient. Chemorepellant= away from source/down gradient

24
Q

What shapes the nephron?

A
  1. Regulate orientated cell division during embryonic development (anisotropic growth)
  2. Cell rearangement/ intercalation (convergent-extension)

anisotrophy= growth rate different in different directions

  1. Theres lots of proliferation after birth, and cells grow along the long axis not the circumference, so theres unequal growth rates. The mitotic angle is always less than 30, influencing the direction of growth
  2. renal tube diameter decreases from 11-12 cells to 3-4 during embryonic development- this would inc tube length while decreasing diameter.
25
Q

Why is the shape of the nephron important- polycystic kidney disease

A

Renal tubes should be long and thin. V important. Polycystic kidney disease comes from mitotic angle being random (as opposed to being less than 30) resulting in fat tubes. Start forming large cysts. Fat tubes results in nephron loss and kidney failure

Cells To Organisms (8 decks)

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