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BMS381 Developmental Neurobiology > L10 - Hypothalamus Development > Flashcards

L10 - Hypothalamus Development Flashcards

1
Q

what are most CNS neurones found in

A

Layers and columns

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2
Q

The fact neruons are found in layers suggests what?

A

Development along the AP and DV axis

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3
Q

3 examples of where layers are present

A

Spinal cord
Cortex
Retina

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4
Q

Layers of the cortex

A 
Molecular
EGL (granular)
Pyramidal 
IGL
Ganlionic layer 
Polymorphic cell layer
White matter
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5
Q

Describe the program cortical cells obey during neurogenesis

A

Inside first - outside last

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6
Q

Three layers of the retina

START CLOSEST TO THE PIGMENTED RETINA

A

Outer neruoblatic layer
Inner neuroblastic layer
Innermost neuroblastic layer

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7
Q

Does the hypothalmus obey the normal rules of development?

Describe it?

A

NO

Neurons found in clusters - nuclei

Arranged in a bewildering patchwork manner with no distinct patterns

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8
Q

What does the hypothalamus control

A

Homeostasis

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9
Q

FIVE examples of things that the hypothalamus controls

A 
Temperature
Circadian cycle 
Electrolyte balance
Sleep 
Sex
Mood 
Growth 
MEtabolism
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10
Q

Where did the first clue about hypothalamic development come from?

A

Loss of function Shh function

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11
Q

Describe what was seen in the Shh loss of function mutatnt

A

Failure of hypothalamic development

Cyclopia - holoprosencephaly

VENTRALISATION

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12
Q

What did a SEM reveal about the Shh mutant

A

Absence of the hypothalamus in KO mouse

Eye field and lateral mesenchyme fail to resolve bilaterally

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13
Q

What do mutations in Shh leead to in humans

A

Cyclopia/holoporsencephaly

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14
Q

What other mutations could lead to holoprosencephaly

A

Mutations in the Shh signalling pathway

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15
Q

Imolication of Shh focussed attnetion to what part … why?… Where is it?

A

Prechordal mesodrm

Expresses Shh

Underlines the anterior neural tube

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16
Q

Describe Shh expression in the notochord

A

Is initially expressed by the notochord

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17
Q

What does Shh deriviing from the prechordal mesoderm give rise to?

A

Fan-shaped set of cells in the neural plate - directly above

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18
Q

What were the experiments to dtermine Shh was causing the set of fan shaped cells to develop?

A

Surgivally ablate PM –> expect to see no Shh induced

Graft extra PM –> expect ectopic Shh produced

Combine pieced of PM with piece of naive neural tube –> Expect o see Shh induced

Pre treat PM to block Shh and then combine with naive neural tube –> Should prevent effect

Conditional knockdown of Shh in PM

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19
Q

Steps when determining what experitments

A

TISSUE - ablate/ectopic/mixing

GENE - knockout/overexpress

20
Q

These experiments of Shh in the PM focussed attnetion on …

A

Ventral midline of the forebrain - floor plate like strucuture

21
Q

Does Shh continue to be expressed all of the way to the end of the nueral tube

A

NO

22
Q

What is the strucutre seen most anteriorly in early stages of hypothalamus development

A

Altar plate

23
Q

What are the strcutres seens ANTERIOYL adjacent to the ‘floor plate’ and POSTERIORLY to the ‘floor plate’?

A

Antero-basal

Basal plate

24
Q

What TF is expressed in the floor plate

A

Foxa2 - turns on Shh

25
Q

Why was it thought Shh was acting as a morphogen ….

A

For first 0.5 days (chick) genes expressed

26
Q

What gene was seen in the Altar plate - furthest from Floor plate

A

Pax6

Seen in low concentratiosn to Shh

27
Q

What genes are seen in response to intermediate Shh signalling

A

Nkx2.2

28
Q

Describe what happens to the Shh morphogen model after 0.5 days in the chick

A

Model just falls apart

Rapidly obscured

29
Q

How did we see that the model had fallen apart —-

A

Using antisense strands to known progenitor markers (IN SITU) … shows a chaotic clustering on the edge of the floor-plate basal-plate territory

Patterns coud not be explaind by simple Shh

30
Q

Instead … After day 0.5 we see the PM begin to turn on …

A

BMP and pSMAD157
THEN the BMPS act on their on cell to turn ON
FGF10 (and components e.g. pea3)

31
Q

Why is it weird for Shh+ cells to be expressing BMP

A

They usually repress each other

32
Q

For a short time the fan like cells xpress (3)

A

Shh, BMP7 and FGF10

33
Q

What is the effect of the cells turning on FGF10

A

Turn on cycling genes - cells become hugely proliferative

34
Q

What experiment was conducted by Fu et al. to study the movement of FGF10+ cells - describe results

A

Fate mapping shows that the FGF10+ cells grow and give rise to an extensive part of the ventral hypothalamus

35
Q

What was Fu et al, hypothesis wrt the FGF10++ccells

A

They are unusual so are these the cells giving rise to the hypothalamus

36
Q

What model was proposed by Fu of the growth of the hypothalamus

A

Sequential anisotropic growth model of hypothalamuc development

37
Q

Describe the Sequential anisotropic growth model of hypothalamuc development

A

FGF10+ cells proliferate to give two daughters

ONE same - FGF10+
ONE downregulates FGF10+ and is displaced anteriorly to form the anterior hypothalmus

THEN THERE IS A SWITCH

Same thing happens but now one daughter is displaced POSTERIORLY - downregulates FGF10 and forms the mammillary hypothalamus (posterior)

38
Q

During hypothalamic development what is special about the FGF10+ cells

A

There are always a constant number - this DOESNT change

39
Q

What happens to the early patterning effect of Shh

A

It is obscured by the growth of cells from the FGF10+ progenitor cells

40
Q

Where does the PVN come from

What are the conditions here

A

Alter plate

Pax6+ and low Shh

41
Q

Where does the medial eminence and posterior pituitary come from

A

The basal plate expressing Shh and FGF10

42
Q

Where does the ARC, LH, SCN and VMN come from

A

Mixture - intermediate levels of shh

43
Q

SCN invoved in

A

Super chiasmatic nucleus

44
Q

ARc involved in

A

Eating

Repro

45
Q

TMN, LH involved in

A

Sleep-wake cycle

46
Q

why was it thought there was a hypothalamic stem cell

A

Since throughout development a constant number of FGF10+ cells need to be maintained

BMS381 Developmental Neurobiology (16 decks)

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