Anterior vs posterior

Question 1

What are the anterior fates of the embryo?

Answer 1

The forebrain

Question 2

What are the posterior fates of the embryo?

Answer 2

The hindbrain and spinal chord

Question 3

What 3 components is the nervous system made of?

Answer 3

1) CNS
2) PNS
3) Enteric nervous system

Question 4

What is the CNS comprised of?

Answer 4

• Brain
• Spinal chord
• Specialised sensory derivatives derived from forebrain tissue (eg. retina, olfactory, taste receptors)

Question 5

Where are all the components of the nervous system derived from?

Answer 5

From the neural plate of the line of cells which lie on the boundary between the neural plate and the surface ectoderm (the neural plate border)

Question 6

When does the neural plate form in embryogenesis in humans?

Answer 6

Week 3-5

Question 7

How do we know that all the main different parts begin to be established early on in embryogenesis?

Answer 7

Can ‘tag’ specific molecules using antibodies, complimentary to proteins expressed:

Reveals organisation/regionalisation/development of specific regions

Not all the cells are the same - different transcriptional profile and therefore different proteins

Question 8

What does convergent extension cause?

Answer 8

• Anterior endoderm and prechordal mesoderm to lie underneath one end of the neural plate
• Notochord to lie underneath the other end

Question 9

How are the signals secreted from the anterior endoderm and axial mesoderm different?

Answer 9

TFs from the anterior endoderm and prechordal mesoderm induce ANTERIOR-TYPE transcription factors in the overlying neural plate cells

TFs from the notochord induce POSTERIOR-TYPE transcription factors in the overlying neural plate cells

Question 10

What is sox2?

Answer 10

A highly conserved transcription factor which are expressed in cells that are on their way to adopt a neural fate

Question 11

Where are sox2s expressed and when?

Answer 11

• In the neural plate
• Later confined to the forebrain (telencephalon, diencephalon)
• Just after the anterior endoderm/ prechordal mesoderm has involuted

Question 12

What do TFs, such as sox2, determine?

Answer 12

Anterior fate of the neural plate

Question 13

How does the neural plate get longer?

Answer 13

ACTIVATION-TRANSFORMATION MODEL:

• Signals from the notochord (underneath the neural plate) cause the back end of the neural plate to proliferate - BMPS?
• At the same time, DIFFERENT signals from the notochord transform these cells from an anterior to a posterior identity (represses Ant TFs) - Wnt, FGFs, RA etc

Question 14

What is the ‘anterior CNS’?

Answer 14

Forebrain (telencephalon, diencephalon) and brain derivatives (eg. optic nerve)

Question 15

What is the ‘posterior CNS’?

Answer 15

Hindbrain and spinal cord

Question 16

How are BMP antagonists maintained in the prechordal mesoderm?

Answer 16

• By transcription factors siamois and goosegoid

Question 17

In the anterior endoderm, what is induced by siamois and goosegoid and what do these molecules do?

Answer 17

Secreted molecules cerberus, frzb, dickkopf

Which inhibit the Wnt signalling pathway

Question 18

What is needed in order to get anterior neural plate cells?

Answer 18

Inhibition of BMP AND Wnt signalling, by BMP and Wnt antagonists from the axial mesoderm

Question 19

Where is Wnt signalling repressed?

Answer 19

In the neural plate, directly above the anterior endoderm

Question 20

What do FGFs do and where are they high/low?

Answer 20

Maintain the proliferation of cells

Highest at the posterior end of the neural plate, low at the anterior - forms a gradient

Question 21

What happens to Wnts at the notochord extends?

What does this form?

Answer 21

Wnts are upregulated

Forms a gradient, where Wnts are low anteriorly and high posteriorly

Question 22

What causes the neural plate to posteriorise?

Answer 22

Upregulation of FGFs, Wnts and RA in a gradient manner as the notochord extends

Question 23

Where does the extreme anterior fate arise? (forebrain)

What signal allows this?

Answer 23

Where there is NO Wnt signalling AT ALL

• Signals from the anterior endoderm (cerberus)
• Inhibits BMPs, Wnts and Nodal

Question 24

What does retanoic acid do?

Answer 24

• Diffuse through the membrane and becomes bound by a cytoplasmic receptor
• When bound, goes through the pores in the nucleus adn binds to the promoters of genes
• Regulates gene transcription of HOX genes

Question 25

What happens when RA is expressed in high concentrations compared to if low concentrations?

Answer 25

- Different subset of TFs turned on, dependant on the concentration of RA that the cells see

Question 26

How is a gradient in the nervous system turned into step-like units (segmented)? What model is this?

Answer 26

- Lewis Wolpert model - X axis is distance from the source - Y axis is concentration of the molecule - Different cells respond differently to different threshold concentrations of the molecule by adopting different fates in a stepwise identity (in relation to low, medium and high concentration)

Question 27

What organisms is segmentation first seen in?

Answer 27

Segmented worms and drosophila larvae

Question 28

What is segmentation controlled by in drosophila larvae and how?

Answer 28

Hox genes - expressed in different segmentation patterns in the forming embryo, control the segment identity of each domain

Question 29

How do we know that hox genes specify AP segment identity in drosophila and provide positional information?

Answer 29

- Many different Hox genes - Hox genes are evolutionarily conserved across species (with each hox gene having a homologue) - Each hox gene is expressed in a specific region along the AP axis (from early stages of development through to adulthood) - Up-regulated in response to RA

Question 30

What are Hox gene up-regulated in response to?

Answer 30

Retanoic acid

Question 31

Which Hox gene is turned on in responce to very high RA levels?

Answer 31

Hox 11

Question 32

Which Hox gene is turned on in responce to very low RA levels?

Answer 32

Hox 5

Question 33

What do Hox genes do?

Answer 33

Set the identity of the segment - tell which nerves to form (thoratic, lumbar, sacral,caudal etc)

Question 34

What causes segmentation of the drosophila nerual axis?

Answer 34

- Retanoic Acid concentration gradient from low at the anterior end, to high at the posterior end - Different levels of RA determines which Hox genes are upregulated (expressed) - Changes the transcriptome, fate and function of that cell - Different Hox genes confer different identities to the segment, in regards to neurons etc

Question 35

What happens if knock out the genes which code for Hoxa1 and Hoxb1? What does this show?

Answer 35

- Fail to get rhombomere 4 - Fail to get facial neurons - Shows that Hoxa1 and Hoxb1 are required to specify rhombomere 4

Question 36

What are rhombomeres?

Answer 36

'Bulges' of the developing brain

Question 37

What induces midbrain cells?

Answer 37

An interaction at the boundary between the forebrain and hindbrain cells

Question 38

Why are there multiple Hox genes which all code for the same protein in humans?

Answer 38

As a 'back up' incase one Hox gene fails

Question 39

In the embryo, where does Sox2 eventually become confined to?

Answer 39

The forebrain - diencephalon, telencephalon

Question 40

What does cerberus do?

Answer 40

Inhibits Wnt, BMP and nodal Induces extreme anterior fate - forebrain

Question 41

What does the procencephalon become?

Answer 41

- Dienchephalon | - Telenchephalon

Question 42

What is the procencephalon?

Answer 42

Developing forebrain

Question 43

What does the rhombencephalon become?

Answer 43

Metencephalon | Myelencephalon

Question 44

What is the rhombencephalon

Answer 44

Developing hindbrain