L10 - Hypothalamus Development

Question 1

what are most CNS neurones found in

Answer 1

Layers and columns

Question 2

The fact neruons are found in layers suggests what?

Answer 2

Development along the AP and DV axis

Question 3

3 examples of where layers are present

Answer 3

Spinal cord
Cortex
Retina

Question 4

Layers of the cortex

Answer 4

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

Question 5

Describe the program cortical cells obey during neurogenesis

Answer 5

Inside first - outside last

Question 6

Three layers of the retina

START CLOSEST TO THE PIGMENTED RETINA

Answer 6

Outer neruoblatic layer
Inner neuroblastic layer
Innermost neuroblastic layer

Question 7

Does the hypothalmus obey the normal rules of development?

Describe it?

Answer 7

NO

Neurons found in clusters - nuclei

Arranged in a bewildering patchwork manner with no distinct patterns

Question 8

What does the hypothalamus control

Answer 8

Homeostasis

Question 9

FIVE examples of things that the hypothalamus controls

Answer 9

Temperature
Circadian cycle 
Electrolyte balance
Sleep 
Sex
Mood 
Growth 
MEtabolism

Question 10

Where did the first clue about hypothalamic development come from?

Answer 10

Loss of function Shh function

Question 11

Describe what was seen in the Shh loss of function mutatnt

Answer 11

Failure of hypothalamic development

Cyclopia - holoprosencephaly

VENTRALISATION

Question 12

What did a SEM reveal about the Shh mutant

Answer 12

Absence of the hypothalamus in KO mouse

Eye field and lateral mesenchyme fail to resolve bilaterally

Question 13

What do mutations in Shh leead to in humans

Answer 13

Cyclopia/holoporsencephaly

Question 14

What other mutations could lead to holoprosencephaly

Answer 14

Mutations in the Shh signalling pathway

Question 15

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

Answer 15

Prechordal mesodrm

Expresses Shh

Underlines the anterior neural tube

Question 16

Describe Shh expression in the notochord

Answer 16

Is initially expressed by the notochord

Question 17

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

Answer 17

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

Question 18

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

Answer 18

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

Question 19

Steps when determining what experitments

Answer 19

TISSUE - ablate/ectopic/mixing

GENE - knockout/overexpress

Question 20

These experiments of Shh in the PM focussed attnetion on …

Answer 20

Ventral midline of the forebrain - floor plate like strucuture

Question 21

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

Answer 21

NO

Question 22

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

Answer 22

Altar plate

Question 23

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

Answer 23

Antero-basal

Basal plate

Question 24

What TF is expressed in the floor plate

Answer 24

Foxa2 - turns on Shh

Question 25

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

Answer 25

For first 0.5 days (chick) genes expressed

Question 26

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

Answer 26

Pax6 Seen in low concentratiosn to Shh

Question 27

What genes are seen in response to intermediate Shh signalling

Answer 27

Nkx2.2

Question 28

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

Answer 28

Model just falls apart Rapidly obscured

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

They usually repress each other

Question 32

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

Answer 32

Shh, BMP7 and FGF10

Question 33

What is the effect of the cells turning on FGF10

Answer 33

Turn on cycling genes - cells become hugely proliferative

Question 34

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

Answer 34

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

Question 35

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

Answer 35

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

Question 36

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

Answer 36

Sequential anisotropic growth model of hypothalamuc development

Question 37

Describe the Sequential anisotropic growth model of hypothalamuc development

Answer 37

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)

Question 38

During hypothalamic development what is special about the FGF10+ cells

Answer 38

There are always a constant number - this DOESNT change

Question 39

What happens to the early patterning effect of Shh

Answer 39

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

Question 40

Where does the PVN come from What are the conditions here

Answer 40

Alter plate Pax6+ and low Shh

Question 41

Where does the medial eminence and posterior pituitary come from

Answer 41

The basal plate expressing Shh and FGF10

Question 42

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

Answer 42

Mixture - intermediate levels of shh

Question 43

SCN invoved in

Answer 43

Super chiasmatic nucleus

Question 44

ARc involved in

Answer 44

Eating | Repro

Question 45

TMN, LH involved in

Answer 45

Sleep-wake cycle

Question 46

why was it thought there was a hypothalamic stem cell

Answer 46

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