Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecular + Cellular Neuro > Brain Development > Flashcards

Brain Development Flashcards

1
Q

State the cerebral hemisphere’s (cortex) function (3)

A

receives sensory inputs (e.g. visual & auditory)

controls voluntary motor outputs

association areas (higher mental activities)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hypothalamus function (1)

A

essential for control of homeostatic processes
e.g. temperature, thirst, appetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Pituitary gland function (1)

A

linked with endocrine system via hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Cerebellum function (1)

A

coordinates muscle movements, maintains posture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Medulla function (1)

A

vital physiological processes of the autonomic nervous system e.g. breathing & heart rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can we study brain development? (5)

A

we don’t have direct access to the developing brain in a foetus = look at animals

-Basic brain organisation is the same in all vertebrates

-structurally different

  • similar regions conserved

birds
reptiles
amphibians
mammals
bony fish
shark
lamprey
= animal models

fundamental processes + steps can be studied in diff model organisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do you make a brain? (5)

A

Step 1: Neural induction - v early embryo, after gastrulation, brain develops from this -> 3 primordial layers (ectoderm = brain, mesoderm = muscle, endoderm =gut)

Step 2: Neural tube formation - forms the whole CNS of an embryo

Step 3: Subdivision in specific domains along the anterior-posterior axis (A-P patterning) - specialised regions

Step 4: Neurogenesis: Generation and expansion of new neurons

Step 5: Connecting neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How can you monitor neural induction in an animal model? (4)

A

In chicks:
- use electron microscopy = view the disc using ISH too to view early embryo

  • see diff gene pattern (neural in nature) = forms CNS
  • SOX2 = early markers of development (neural tissue) -> very strongly expressed in medial part of embryo -> these are the cells that are induced to become CNS
  • also look at Delta1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe neural tube formation (5)

A

1) flat disc undergoes neural induction

2) infolding occurs(structural alterations): the middle neural tissue folds into itself

3) This further invaginates into the embryo

4) Eventually connects at the top

5) Forms complete tube that has internalised into embryo (neural tube)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name the neural tube subdivisions (4)

A

Embryo precursors -> Adult:

Prosencephalon -> forebrain

Mesencephalon -> midbrain

Metencephalon -> hindbrain

Myelencephalon -> spinal cord

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe anterior posterior patterning (2)

A

Establishment of different brain regions occur, which overtime develop further into these specialised regions of CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe dorso-ventral patterning (2)

A

Different neuronal identities are established along the dorsal-ventral axis of the neural tube

  • section of spinal cord -> immunostaining shows the different markers of the diff cell types
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are key regulators that cause patterning of the neural tube? (2)

A

Secreted morphogens from secondary organisers (= specialised cell types in the dev. embryo) establish signalling gradients that determine cell fate

Homeotic genes e.g. those encoding homeobox transcription factors impart regional/segmental identity and position secondary organisers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Define morphogen (1)

A

A secreted factor that functions at a distance from its source to directly influence cell fate in a dosage dependent manner

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the “French flag model”? (4)

A

Each cell has the potential to dev as blue, white or red

position of each cell is defined by conc of morphogen

positional value is interpreted by the cells which differentiate to form a pattern
= french flag

they develop diff identities depending on how far they are from the morphogen -. eg closest receive high conc of morph and furthest receive lowest conc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain the morphogen SHH (3)

A

the SHH gene encodes for the sonic hedgehog protein

it’s secreted molecule produced from the ventral neural tube all along to the developed spinal cord

this is critical for DV patterning of CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

describe SHH and eye positioning (3)

A

the splitting of the eye field allows for the formation of the 2 separate eyes

inhibition of SHH shifts eye position: immediately the eyes move medially (w/ decreased SHH) = this is due to a genetic mutation that disrupts SHH production/exposure to specific pharm/natural compounds that inhibit SHH signalling

Loss of SHH/ v v lowe levels = cyclopia and loss of ventral neuronal fates <- no SHH produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do we make specific neurons in the lab? (5)

A
  • making neurons may be useful for regenerative med
  • using ES cells -> we can configure the fate by treating them with either SHH or an SHH antag (Cyclopamine WNT)
  • SHH = Ventral fate
  • Cyclopamine = dorsal fate
  • undergoes WNT signalling
  • Gli3R is a biomarker of tissue growth and inactivation of it = mutant phenotypes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe A-P patterning of the embryo in regards to the structure of the head (5)

A
  • Dkk1-/- embryos are head-less
  • WNT antagonists are required for head formation -> = Wnt signalling = headless, thus the whole head structure is completely dependent on INHIBITION of WNT signalling by secreted WNT antagonist
  • WNT antagonists e.g. Dickkopf
  • low to high WNT + high to low antag. = forebrain, midbrain, (hindbrain), spinal cord
  • Fly → Frog → Chick and mouse (highly conserved process)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How are different brain regions established along A-P axis? give an example (2)

A
  • Homeotic genes encode transcription factors e.g.
    Homeobox (HOX) transcription factors

-Homeotic genes in Drosophila: WT vs mutant w/ fully developed legs in the place of the antennae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe the specific homeotic genes in vertebrate neural tube (4)

A

Otx2 is essential for the Forebrain and Midbrain

Gbx2 is essential for Hindbrain and spinal cord

  • Otx2 and Gbx2 work in a complementary pattern (antagonistically)

Cross-repressive activities establish and maintain a sharp expression boundary between the mesencephalon and r1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Explain the IsO regulatory network (4)

A

Otx2 - r1 = fore + mid brain
Gbx2 - ar1 = hindbrain + spinal cord

A secondary organiser, the IsO, that produces FGF8 is established at the mes/r1 boundary:

Otx2 inhib Fgf8 expression
Gbx2 <-> Fgf8 (maintain each other’s expression)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What do Gbx2-/- embryos lack? (1)

A

They lack the cerebellum

  • seen in mice: midbrain still forms but lack cerebellum when the GBX2 gene is completely deleted
24
Q

Name some secondary organisers and their functions (4)

A

Several secondary organisers refine the
anterior-posterior specification of neural tube territories

key organisers:
- ANR: Anterior neural ridge - produces FGF8
- ZLI: Zona limitans intrathalamica - expresses SHH
- IsO: Isthmus organiser - produces FGF8

25
Q

What happens as a result of Fgf8 loss? (2)

A

Fgf8 loss results in defects in gastrulation and early embryonic lethality because it is also important in the cranial facial structure formation

(seen in The Isthmus (mid-hindbrain organiser))

26
Q

How can we bypass these early defects to study the function
of Fgf8 during later stages of development? (2)

A

Cre/loxP technology!

  • carries out deletions, insertions, translocations + inversions at specific sites in the DNA, at specific times in development = DNA modification that can be targeted by external stimuli
    ==> bypass the early embryo lethality probs
  • Cre: site-specific DNA recombinase
    “molecular scissors
27
Q

Describe Conditional knockouts: Cre/loxP technology (6)

A

1) Floxed gene
2a) Add Cre
2b) minus Cre
3a) + Cre = defective gene
3b) Transcription = Normal mRNA
4a) Transcription = mRNA encoding defective protein

28
Q

Conditional knock-outs mouse eg (3)

A

1) Mouse carrying Cre recombinase gene controlled by tissue specific promoter X (Mes/r1-specific Promoter)

2) Mouse carrying conditional (floxed) alleles of gene Y (Fgf8 exon 3)

1 + 2 = Gene Y is inactivated by Cre in tissue X (Mes/r1-specific gene Fgf8 deletion)

29
Q

Explain En1cre activity in early mes/r1 (3)

A

1) Rosa26 —-STOP—-lacZ

2) w/ Cre expression only in mes/r1

3) = lacZ expression in mes/r1 and derivatives

30
Q

What is Fgf8 necessary for? (3)

A

Fgf8 is required for survival + development of the midbrain and
cerebellum

  • seen in cre/lox mice:
  • control: Cre expression only
    in mes/r1
  • Fgf8 cko: Fgf8 loss only in mes/r1, All other tissues maintain normal Fgf8 expression
31
Q

What is Fgf8 is sufficient to induce? (2)

A

Fgf8 is sufficient to induce mes/r1 identity

= this was enough to induce the dev of structures resembling cerebellum when (ectopically applied to the diencephalon)

32
Q

Summary 1(3)

A

 A-P patterning of the neural tube establishes distinct territories

 A-P patterning is coordinated by the action of
secreted morphogens, homeobox (and other) transcription factors

 D-V patterning likewise establish distinct territories and neuronal identities along the D-V axis; established by the action of morphogens like SHH and transcriptional regulators like Gli3

33
Q

Define Neurogenesis (1) and talk about NSC’s (2)

A

The generation/expansion of new neurons

  • Neural stem cells are known as radial glial cells because they extend to the peel surface of dev CNS (you can see translocation of nucleus that undergoes cell division = interkinetic nuclear migration)
  • NSCs self-renew (maintain NSC pool) through symmetric or asymmetric division
34
Q

what are the 2 types of cell division in the neurogenic cell? (2 +1)

A

symmetric mitosis: radial glial cells expand the population of these cells = increases the pool of available neurogenic cells.

asymmetric mitosis: generate another radial cell (maintain the population of the radial glial cells) but then generate a neuronal precursor = postmitotic neuronal precursors that will migrate up towards the peel surface + essentially start differentiating into mature neurons

these neural stem cells essentially self renew so they can maintain the neural stem cell pool either through symmetric or asymmetric cell division.

35
Q

Name the layers of the developing cortex (3)

A

inner surface = ventricular zone (next to ventricle)

just outside this = sub-ventricular zone

cortical plate outside that

36
Q

Why is the ventricular zone important? (1)

A

neural stem cells that give rise to new neurons are localised here = neurogenic zone of the developing cortex

37
Q

Name the 2 main cortical neurons (3)

A

Two major classes of neurons: excitatory (glutamatergic) and
inhibitory (GABA-ergic) neurons:

  • Pyramidal neurons are Excitatory (glu)
  • Interneurons are Inhibitory (GABA)
38
Q

Explain how Glutamate- and GABA-ergic neurons are born in different parts of the embryonic brain (3)

A
  • Glutamatergic neurons produced in the dorsal part of the forebrain (pallium) migrates radially into the developing cortex (using SHH)
  • GABA-ergic neurons produced in the ventral part of the forebrain(subpallium) migrates tangentially to the pallium to integrate into the cortical circuitry

LGE: Lateral Ganglionic Eminence = produce interneurons

MGE: Medial GE

39
Q

Explain Glutamatergic progenitors migration (+settling) (3)

A

Glutamatergic progenitors migrate radially and different
populations, born at different developmental time points, position themselves in an “inside-out” fashion

Late-born neurons settle in the outer layers

Early born neurons settle in the deep layers of the cortex
(‘inside out’)

  • so they migrate up to the peel surface and place themselves above the already generated neurons
40
Q

What happens to Reeler mutants? (1)

A

Reeler mutants (mouse mutant) fail to undergo “preplate splitting” and have an inverted cortical organisation

41
Q

Summary 2 (4)

A

 New neurons are generated from neuronal stem cells

 Different classes of neurons are born in distinct embryonic regions e.g. glutamatergic neurons (forebrain pallium and cerebellar rhombic lip) and GABA-ergic neurons (forebrain subpallium and cerebellar ventricular zone)

 Neuronal progenitors migrate to their final position

 Migratory cues are essential for normal brain development and architecture

42
Q

Name some facts about neurons (4)

A
  • Adult brain has 86 billion neurons
  • Each neuron makes 7,000 connections with other neurons
  • Total complexity = 100-500 trillion connections for transferring
    info
  • 100 billion galaxies x 200 billion stars = 2,000 billion stars
43
Q

How does Axon guidance work and name some molecules (2)

A

Works through a process of attraction and repulsion of molecules to help guide developing axons to the necessary source

eg of molecules:
- slit
- netri
- semaphorin
- ephrin
- DCC
- Robo
- Plexin
- Met
- L1
- Neuropilin
- Eph

44
Q

Define Synaptogenesis (3)

A

the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person’s lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis

  • defects in this development can cause many disorders
45
Q

Name some developmental brain defects and their causes (6)

A

 Neurulation - spina bifida

 Micro- or macrocephaly

 Transformation, Aplasia or hypoplasia of specific regions e.g. cerebellar vermis hypoplasia (patterning)

 Lissencephaly and heterotopia (migration)

 Axon tract agenesis or mis-routing (axonal transport)

 Altered connectivity and/or excitatory:inhibitory balance ( altered connectivity = autism)

46
Q

Name some Human syndromes with cerebellar defects (5)

A

Joubert syndrome

Dandy-Walker malformation

Ponto-cerebellar hypoplasia

Cerebellar vermis hypoplasia

Rhomb- encephalosynapsis

47
Q

Explain CHARGE syndrome (4)

A

1/8,000- 1/12,000 incidence -caused by an autosomal dominant congenital malformation

*Coloboma of the eye
*Heart defects
*Atresia of the choanae
*Retardation of growth and development
*Genito-urinary abnormalities
*Ear abnormalities

Brain defects:
*Hypoplasia of the inferior cerebellar vermis, brain stem
*Cerebellar heterotopia
*Olfactory bulb hypoplasia

*High (estimated 27.5%) of patients are autistic

48
Q

Explain Vermis defects in CHARGE
syndrome (3)

A

This is vermis hypoplasia = incomplete development or underdevelopment of cerebellar vermis

= all children w/ this = dev. delays (80% severe, 20%
moderate)

  • Reduced FGF signalling from the IsO results in vermis hypoplasia
49
Q

What do we see in CHARGE models? (2)

A
  • Fgf8 expression is reduced in mouse models of CHARGE syndrome
  • Chd7 interacts with Fgf8 to cause cerebellar vermis hypoplasia
50
Q

Describe Lissencephaly (4)

A

 Smooth cortex, lack of gyri (agyria), broad, thick gyri(pachygyria) and neuronal heterotopia (cells in abnormal positions)

 Caused by abnormal neuronal migration

 Mutations in LIS1, DCX (Doublecortin)

  • Autosomal recessive lissencephaly with cerebellar hypoplasia: depicts severe abnormalities of the cerebellum, hippocampus + brainstem maps due to Mutations in RELN
51
Q

What are Corpus callosum defects? (2)

A

a defect caused by axon guidance

  • either incomplete formation of corpus callosum or not formed at all
52
Q

Describe Autism spectrum disorders(6)

A
  • 1% of US children (3-17yrs) diagnosed with ASD
  • Fastest-expanding developmental disability (from
    1/150 (2007) to 1/110 (2009))
  • 40% of children with autism do not speak
  • Neuroanatamical abnormalities observed include
    cerebellar hypoplasia and expanded pre-frontal cortex
  • Complex genetic inheritance, more than 300 genes
    implicated
  • Many genes are linked to synaptogenesis suggesting that synaptic dysfunction and defective connectivity might underlie a subset of ASD cases
53
Q

What are some genes implicated in ASD? (3)

A

number of proteins thought to be highly likely to be involved in synaptogenesis problems -. causing autism

BUT also genes:
eg SCN2A, SHANK3, CH83

-Many high confidence ASD risk genes encode chromatin regulators

54
Q

Summary 3 (1)

A

Neurodevelopmental disorders can result from developmental defects in brain patterning, neurogenesis and growth, neuronal migration, axon pathfinding and synaptogenesis

55
Q

What is the future? (4)

A

 Human brain development

 The aetiology of many neurodevelopmental disorders remain unknown

 Can we treat any of these disorders e.g. those caused by synaptogenesis defects?

 How do environmental factors affect brain
development?

Molecular + Cellular Neuro (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions