Organogenesis Flashcards

1
Q

What are the two building blocks of the kidney?

A

nephron + collecting duct

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2
Q

Where does the collecting duct originate from?

A

ureteric bud

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3
Q

Where do the nephrons originate from?

A

metanephric mesenchyme

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4
Q

Which part of the mesoderm does the kidney originate from?

A

the intermediate mesoderm

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5
Q

What proteins are involved in kidney development?

A

Lim1 (homeodomain TF)
Pax2 and Pax 8 (paired box TFs)

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6
Q

How are kidney tissues initially induced?

A

a signal from the paraxial mesoderm to the intermediate mesoderm (paracrine signal), molecular nature of this signal is currently unknown
AND a signal from lateral side of the embryo (paracrine signal), BMP2

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7
Q

What is BMP2 and how does it work?

A

it is a secreted morphogen that induces kidney tissue at a ‘medium level’ of activity
(i.e. switches on Pax2/Lim1 at medium conc)

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8
Q

How do the UB and MM ensure growth and development remain proportionate?

A

through local reciprocal inductive interactions, a two way conversation between cells
one cell (inducer) regulates behaviour of another cell (responder)
each cell is changed

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9
Q

What is the signal and what is the receptor involved in the branching of the ureteric tree?

A

signal: glial cell line-derived neurotrophic factor (GDNF), active in the MM
receptor: Ret, expressed in the nephric duct and tips of ureteric branches

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10
Q

What results if either the receptor or signal is removed during development of the nephric duct?

A

no budding or branching of the nephric duct

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11
Q

GNDF is both necessary and sufficient for budding/branching. True or False?

A

True

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12
Q

The ureteric bud tip swells and forms how many branches?

A

2 (occasionally 3) called bifurcation
branch extends and bifurcates again in a reiterative process
caused by an exogenously localised source of GDNF

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13
Q

How is the ureteric bud tip domain formed?

A

ret signalling mediates rearrangement of epithelial cells before budding to form domain

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14
Q

What signal induces mesenchymal-to-epithelial transition (MET) in the metanephric mesenchyme?

A

Wnt9B, which is secreted from the ureteric bud (paracrine signal)

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15
Q

What does Wnt4 do in the MM?

A

acts in an autocrine manner to propagate mesenchymal aggregation
renal vesicle continues to grow until Wnt4 concentration threshold is detected by quorum sensing
only then does RV begin to differentiate

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16
Q

What are some aspects that develop during MET of the MM in the kidney?

A
  • generation of a tubular shape which form a lumen (single cell layered, non-stratified epithelium)
  • development of adhesion junctions (cells stick together)
  • establishment of apicobasal polarity
  • development of occluding junction (prevents leaking of tubes)
17
Q

What is a chemoattractant and a what is a chemorepellent?

A

chemoattractant - cells move toward a signal soure (up conc gradient)
chemorepellent - cells move away from a signal source (down conc gradient)

18
Q

Name the main sections of the nephron and state their function.

A

glomerulus - blood filter
proximal tubes - recovery of salt, water, metabolites
loop of Henle - essential in producing (more concentrated urine)
distal tubes - K+, Na+, Ca2+ regulation

19
Q

What is the mechanism of glomerulus development?

A

endothelial cells respond to a signal from vascular endothelial growth factor (VEGF) secreted by podocyte precursor cells
VEGF is a chemoattractant

20
Q

What two methods are used to shape an organ?

A
  1. regulate orientation of cell division during organ growth (anisotropic growth)
  2. organ shape is sculpted by cell rearrangement (eg cell intercalation)
21
Q

What is an example of anisotropic growth in renal tubes?

A

tubules increase in length not diameter, suggests specific orientation of cell division
defects in division lead to formation of cysts

22
Q

What is an example of cell rearrangement in renal tubes?

A

highly ordered cell intercalation increases tubule length and decreases tubule circumference

23
Q

Which tissue secretes GDNF?

A

Metanephric mesenchyme

24
Q

What are the steps of nephron development?

A

-MM cells condense around UB
-Transform into small cysts with epithelial characteristics (renal vesicle)
-Differentiation and morphogenesis, fuses with UB
-Blood vessel progenitors invade and form glomerular capillaries
-Nephron differentiation (specialised transporting segments)