developmental biology of the brain

Question 1

what is gastrulation?

Answer 1

the process where the single layered blastula is reorganised into a trilaminar structure called the gastrula

Question 2

describe the framework for CNS development

Answer 2

• rapidly dividing ball of cells
• signalling centres develop
• cell mixing restricted
• cells destined to be skin or brain

Question 3

once a cell is destined to be neural tissue what occurs?

Answer 3

• neurones are generated and they migrate to final position
• glia are produced
• synapses are generated

Question 4

how many glia are there per neurones?

Answer 4

there are 10 times as many glia cells than neurones

Question 5

once synapses are generated in the CNS what occurs?

Answer 5

excess neurons are culled

Question 6

what occurs in the CNS throughout life?

Answer 6

fine tuning

new synapses are formed and neurones are tested to see whether they need to be maintained

Question 7

what is the neuroectoderm?

Answer 7

it is ectoderm which received bone morphogenetic protein-inhibiting signals from proteins such as noggin, which leads to the development of neural tissue (and not skin)

Question 8

where do the signal to the ectoderm (to become neuroectoderm) come from?

Answer 8

the axial mesoderm, which is ideally placed under the ectoderm for signalling

Question 9

what ensure correct neural plate formation? (3)

Answer 9

• signals expressed in correct location
• signals that are produced have the correct cell type inducing ability
• signals expressed at the correct time

Question 10

what is BMP4?

Answer 10

bone morphogenetic protein 4 is a pro-epidermis and anti-neutralising signal
by default all ectoderm will become skin
this needs to be blocked to form neural tissue

Question 11

what signals block BMP4? (4)

Answer 11

• Cerberus
• chordin
• noggin
• follistatin

Question 12

what is the proposed retinoic acid concentration gradients function?

Answer 12

anterior/posterior signalling

high concentration at the head and low at the tail

Question 13

what signals need to be inhibited to make a head? (3)

Answer 13

• Wnt/B-catenin
• TGF
• BMP

Question 14

what is the neural plate?

Answer 14

neutrally committed, multipotent stem cells

TF expressed are that of a broad domain, restricting cell potency

Question 15

why might making a nock-out mouse for a specific TF in neuronal differentiation not make an effect?

Answer 15

the brain is robust, there is lots of redundancy that will compensate for the lack of TF

Question 16

what TF maintain neural progenitor from differentiating?

Answer 16

Sox 1, 2 and 3

Question 17

which sox gene is important in fate switching?

Answer 17

Sox2 in neural ectoderm inhibits Oct4

Oct4 drives the formation of mesoderm

Question 18

what is sox2 also important for?

Answer 18

localisation of the stomach in the gut

Question 19

Additionally, what is the function of other sox TFs?

Answer 19

to stop stem cell like proliferation and drive neural differentiation

Question 20

along with special and temporal factors, what else effects gene expression?

Answer 20

gender

Question 21

why are mouse embryos hard to work with?

Answer 21

they are hard to culture and need to be looked after

can be cultured for a few days in a bioreactor

Question 22

what can be done to a chick to observe the effect of a TF on nervous system development?

Answer 22

electrophorese a gene into the side of embryo through a window of an egg
the other side of the embryo can be used as a control

Question 23

why are in utero operations difficult?

Answer 23

can easily trigger a miscarriage

Question 24

why are Xenopus embryos useful in developmental studies?

Answer 24

embryos are quite large and easy to manipulate

this means they are useful in telling us about the early stages of development

Question 25

how can the same set of morphogens used in different parts of the embryo produce different tissue?

Answer 25

these signals are acting on cells with different TF profiles. for example, response gene for a signal may be so epigenetically repressed, from a past signal, that there is no response.

Question 26

what happens if neural stem cells are triggered to leave the cell cycle too early by manipulating factors regulating the cell cycle?

Answer 26

brain formed is too small

Question 27

what happens if neural stem cells are artificially kept in the cell cycle for too long before leaving?

Answer 27

lots of neurones will end up being culled

Question 28

how have humans tweaked the cell cycle in the cerebral cortex over evolution?

Answer 28

increased proliferation before differentiation

Question 29

what does the notochord release to induce the anterior/posterior regionalisation of the neural tube?

Answer 29

Shh

Question 30

what are bHLH? and what do they do?

Answer 30

a group of pro-neural TFs, they tell neural stem cells to make neurones

Question 31

what is neurogenin?

Answer 31

a family of bHLH TFs involved in neuronal differentiation

Question 32

name a localised TF for retinal development

Answer 32

bHLH Ath5

Question 33

what does oscillations of bHLH TFs maintain?

Answer 33

multipotency

Question 34

what happens when there bHLH TFs are stably expressed?

Answer 34

differentiation

Question 35

name a pro-neural gene involved in cerebellum development

Answer 35

math1 | FISH can be used to located this marker in early embryonic development

Question 36

in what order are the brain axes formed?

Answer 36

- anterior/posterior - dorsal/ventral - left/right

Question 37

at what point is the DV axis established

Answer 37

shortly after neural tube closure

Question 38

what are the three main regions of the brain?

Answer 38

- hindbrain - midbrain - forebrain

Question 39

what do signalling centres release?

Answer 39

local signals/morphogens

Question 40

name an example of a signalling centre, giving its location

Answer 40

the isthmus is a signalling centre located at the midbrain/hindbrain boundary

Question 41

what will the hindbrain become?

Answer 41

the cerebellum

Question 42

where are dopaminergic neurones located?

Answer 42

in the midbrain at the bottom of the neural tube, they project into the forebrain in later development

Question 43

what happens when you move the location of a signalling centre?

Answer 43

trigger development of the different tissues in the wrong part of the brain

Question 44

name the two key signals released from the isthmus?

Answer 44

FGF8 and Wnt1

Question 45

what occur in Oct2 null mice?

Answer 45

they lack anything in front of the isthmus (brain anterior)

Question 46

what causes DN apoptosis in Parkinson's?

Answer 46

the production of ROS

Question 47

what signals the ventral location of dopaminergic neurones?

Answer 47

Shh

Question 48

what signals the midbrain information of dopaminergic neurons?

Answer 48

FGF8 and Wnts

Question 49

what is the substantia nigra?

Answer 49

it is the location of DN in the midbrain | it is diminished in Parkinson's

Question 50

what happens when SNpc DN die?

Answer 50

tremors and reduced movement | this occurs in Parkinson's

Question 51

what is the function of VTA DN?

Answer 51

they are involved in mood control and addition | they are not affected in Parkinson's

Question 52

what are radial glia?

Answer 52

they are neuronal stem cells that can form DN and later astrocytes to support DN

Question 53

what are astrocytes?

Answer 53

star shaped glial cells of the CNS

Question 54

what's the additional function of radial glial?

Answer 54

act as scaffold for DN to migrate along | DN exit the cell cycle in the ventricular zone and migrate down RG to ventricle edge

Question 55

what does cortical hem secrete?

Answer 55

Wnts and BMP

Question 56

what does cortical anthem secrete and why?

Answer 56

extracellular region of Frizzled recepts, this binds wnt and locally prevents Wnt signalling

Question 57

control of cell type and number is important. which additional factor is especially important in the layered cortex

Answer 57

migration

Question 58

which two cell types are important for this migration?

Answer 58

radial glia and Cajal-retzius cells

Question 59

what is the function of Cajal-retzius cells?

Answer 59

they are not entirely understood but seen to be essential in stopping cell migration

Question 60

what is microcephaly?

Answer 60

congenital condition associated with incomplete brain development

Question 61

which virus is suggested to be causing microcephaly?

Answer 61

Zika virus | this is additionally associated with additional neuronal cell death and even fewer neurons

Question 62

what is used to model microcephaly and show links to Zika?

Answer 62

cerebral organoids | these have organisation much like the cerebral cortex

Question 63

what causes reduced neurone production in microcephaly?

Answer 63

incorrect spindle orientation resulting in not enough symmetrical division of radial glia

Question 64

how many layers are there in the neocortex?

Answer 64

6 | they are not completely independent and need to be in the correct order for function

Question 65

what percentage of neurones in the neocortex are excitatory? name the one type that is inhibitory

Answer 65

80% | GABA interneurons

Question 66

which layer of the cortex is generated first?

Answer 66

the deepest layer | newly generated neurones crawl past these to form upper layers towards meninges membrane guided by radial glia

Question 67

what causes lissencephaly?

Answer 67

a disorder of cortical migration caused by cells not responding correctly to signals and dysfunctional cytoskeletons, resulting in missing/disordered layers of the cortex

Question 68

what is reelin?

Answer 68

protein released by Cajal-retzius cells signalling cells to migrate toward these cells

Question 69

what recent discovery was made about oligodendrocytes using single-cell RNA-seq?

Answer 69

there are 5 types of oligodendrocytes (cells which myelinated neurones), these are the cells which are attacked in MS

Question 70

what causes radial glia cells to produce astrocytes and not DN?

Answer 70

methylation of pro-neural genes histones

Question 71

what is the Blue Brain Project?

Answer 71

they are trying to map the human connectome in order to be able to engineer a novel system