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Neuroscience-special topic > Exam 1: Lecture 1 > Flashcards

Exam 1: Lecture 1 Flashcards

1
Q

Name the 6 development events

A

1) formation and patterning of neural tube
2) neurogenesis
3) migration
4) Cell differentiation
5) Synapse formation
6) Connectivity maturation

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2
Q

The process by which embryonic tissue that will become neural tissue is SPECIFIED is…

A

neural induction

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3
Q

Embryonic neural tissue is the ___ ___ which gives rise to the ____ ____ which gives rise to the whole CNS and the ___ ___ which gives rise to PNS.

A

neural plate

Neural tube - CNS
neural crest- PNS

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4
Q

What is the process by which different regions start to appear in the neural plate/tube?

A

patterning of neural plate/tube

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5
Q

what is the process of formation of the neural tube.

A

neurulation

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6
Q

What is the process by which neural PROGENTIORS (stem cells) rapidly divide to make other progenitors.

A

progenitor proliferation

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7
Q

What are other names for proliferative zone?

A

germinal and ventricular zone

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8
Q

ventricular zone: apical and basal identification

A

apical is on inner space

basal is facing outside

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9
Q

What determines fate of progeny in progenitor division?

A

plane of axis

apical domain: where the division line is

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10
Q

Process by which neural progenitors (neural stem cells) produce neurons

A

neurogenesis

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11
Q

Process by which glial cells are generated by neural progenitors

A

gliogenesis

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12
Q

neuroblasts move out birthplace in proliferative zones of neural tube to final position in NS.

A

Migration

radial or tangential

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13
Q

Process by which newly born cells acquire specific cell type identity and become SPECIALIZED IN FUNCTION

A

cell differentiation

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14
Q

circuit formation and synapse formation: how do they do it

A

specialization at axons/dendrites GROWTH CONES allow them to navigate the tissue, following guidance cues, until they find counterpart

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15
Q

Process by which axons/dendrites reach target

A

guidance/navigation

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16
Q

Axonal growth cones transform into ___ ___

A

presynaptic specializations

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17
Q

Dendrites receive synapses at

A

different locations (not just final ends)

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18
Q

Synaptogenesis

A

synapse formation

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19
Q

Circuit/connectivity maturation

A

process newly form neural circuits reach an stable state )usually referring to acquisition of functionality, but stable state, doesn’t mean final state.

Maturation can extend during long periods

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20
Q

What is MATURATION, not plasticity?

A 
synaptic pruning
synaptic rearrangement
natural cell death 
over-produced neural cells
myelination
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21
Q

Standardized system that provides unified developmental chronology of vertebrate embryo (23 stages)

A

stages are delineated through the development of landmark structures not by size/number days of development, which vary

Human-60 days, then fetus
mouse-E16
rat-E17.5

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22
Q

Early Development

A

induction, neural tube formation, (stage 9-12)

neural tube patterning/segmentation, (stages 12-15)

neural progenitor proliferation (stages 9-22)

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23
Q

mid development

A
  1. neurogenesis starts stages 23 through birth)
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24
Q

late neurodevelopment

A

stages 5 and 6. After GW26, continues after birth, throughout childhood

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25
Q

After induction, what two processes occur SIMULTANEOUSLY?

A

patterning and neurulation

becomes regionalized and folds inward

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26
Q

neural plate induction is specification of the ______ from _____, which occurs in 3-laminat disk of gastrula.

A

neuroectoderm

ectoderm

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27
Q

gastrulation ends with

A

neurulation

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28
Q

inductive (neural) signals

A

chordin, noggin, follistatin

come from underlying mesoderm, NOTOCHORD

vertical

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29
Q

since not all mesoderm tissue has same neural inductive capacity, ________
determines fate in neural plate

A

position of overlying tissue with respect to notochord

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30
Q

anti-neural signals

A

BMP4, Wnt

FLANKING ECTODERM (lateral/planar) induction

repress neural, promote ectodermal

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31
Q

inner cell mass are embryonic cells that do what? What are these specific cells called?

A

generate entire embryo

totipotent stem cells

line right by the inside semicircle

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32
Q

What is part of the BILAMINAR DISK that gives rise to the embryo?

A

Epiblast

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33
Q

What originates in embryonic part of placenta?

A

hypoblast - around the epiblast

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34
Q

Exocoelomic cavity

A

that middle yok sac thing

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35
Q

Main events of the 2nd week of development

A

formation of exocoelomic membrane
stuff goes around

Endometiral gland

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36
Q

What happens in early embryogenesis (before neural induction):

Days 14-15

A

14-15: primitive streak in epiblast. Epiblasts cells migrate inward from the primitive node through the streak (will form mesoderm and endoderm)

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37
Q

What happens in early embryogenesis (before neural induction):

Days 16:

ingressing epiblast cells form ___ and ___. At the midline, will form specialized mesoderm structure called ______

A

form mesoderm and endoderm

notochord

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38
Q

What happens in early embryogenesis (before neural induction):

Gastrulation

A

bilaminar to trilaminar embryo

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39
Q

Signals from ______ are required for induction of neural tissue

A

primary organizers

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40
Q

What is tissue/structure that exert difrentiation effect on the surrounding tissue and make it develop into a different structure (e.g. inducing and entire body axis, or inducing neural fate in the ectoderm).

A

Primary organizer

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41
Q

In animals ______ is the primary organizer

in amphibians ____ of the blastopore is the primary organizers

A

primary node (end of primity streak)

dorsal lip

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42
Q

What are chemical signals that emanate from a specific tissue and spread away from the source creating a concentration gradient that determines the fate of cells exposed to the gradient?

A

morphogens

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43
Q

Neural plate induction

When does the neural plate appear?
What does it cover?

A

Day 17

thickening of embryonic ectoderm over axial mesoderm

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44
Q

Notochord forms only where?

A

midline rostral to primitive node and caudal to oropharyngeal membrane.

Main point: not present along whole axis

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45
Q

What is the axial mesoderm anterior to notochord?

A

prechordal plate (PCP)

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46
Q

Though both the notochord and PCP are patterning the neural plate they have

A

different effects

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47
Q

Are FGFs inductive or antineural?

A

can promote induction at early stages or inhibit neural at later stages

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48
Q

Neural fate signals (review)

A

Chordin
Noggin
Follistatin
FGF

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49
Q

Inhibit neural fate (review)

A

BMP4, Wnt, FGFs

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50
Q

Drosophila homologs:
____ homolog to ____
___ homolog to ____

A

Sog –> Chordin (neural)

Dpp –> BMPs (anti-neural)

51
Q

Pathway: how do Chordin, Noggin, and Follistatin promote neural fate?

A

antagonize BMP signal path (stop it from bbdining

52
Q

Is blocking BMP all that’s needed for neural fate?

A

No, we also need FGF bind to FGFR

That gets ERK and Zic3 going

53
Q

What happens if FGF signaling blocked?

A

no zic3, no neural induction

54
Q

What in BMP pathway inhibits Zic1

A

Smad

55
Q

D-V patterning:

Describe ventral signals

A

Shh; basal plate

released from notochord/PCP

floor plate- develops from tissue with lots of Shh

ventral high/dorsal low gradient

56
Q

D-V patterning:

Describe dorsal signals

A

BMPs

Alar plate
Roof plate

57
Q

After floor plate develops at high Shh gradient, what does it do?

A

releases more Shh to gcreate new gradient so this happens:

neural plate/tube exposed to high Shh becomes ventral neural tube, which develops into basal plate

58
Q

Neural plate exposed to high

concentrations of ___ and ___ is dorsal and develops into ___ plate (sensory)

A

BMPs and Wnt

alar

59
Q

Different dosages of morphogens activate expression of distinct _____ in progenitors, producing specification of progenitors across the neural tube.

A

transcription factors.

Different transcription factors = different progenitors fate, different neurons, different brain structure

60
Q

AP (or rostral/caudal patterning):

What happens to the neural plate/tube that forms above PCP?

A

Anterior neural plate/tube

Gives rise to forebrain.

61
Q

AP (or rostral/caudal patterning):

What happens to the neural plate/tube that forms above notochord?

A

posterior neural plate/tube

Gives rise to brainstem/spinal cord

62
Q

Rostral-Caudal patterning, of CAUDAL/POSTERIOR neural plate/tube

___ from primary node and mesoderm

____ from paraxial mesoderm around are that develops into rhombencephalon (Hindbrain)

____ from paraxial mesoderm

A

FGF

RA (retinoic acid)

Wnts

63
Q

Rostral-Caudal patterning, of ANTERIOR/ROSTRAL

neural plate/tube

A

FGF

Wnt- antagonists

64
Q

______ (border of neural plate) gives rise to neural crest.

A

neural folds

65
Q

the neural plate folds into the neural tube starting at…

A

Anterior NP- posterior NP border

66
Q

What is derived from neural crest?

A

PNS neurons

AND non-neural elements

AND pharyngeal arches: cranio-facial development

67
Q

What forms from rostral/anterior end of neural tube

A

encephalon- brain

Prosencephalon-forebrain
Mesencephalon- midbrain
Rhombencephalon- hindbrain

68
Q

What forms from caudal/posterior

end of neural tube

A

spinal cord

69
Q

What forms during 1st phase of differentiation?

A

Prosencephalon-forebrain
Mesencephalon- midbrain
Rhombencephalon- hindbrain

primary vesicles (3 vesicles- 4th week)

70
Q

Second phase of differentiation

A

secondary vesicle (5 vesicles, 8 weeks)

Prosencephalon –> telencephalic vesicle (pair0 and diencephalon

rhom –> metencephalon and myelencephalon

Also: optic vesicle sproat to become optic stalk and cups. Ultimately becomes optic nerve and retina

71
Q

______ triggers the formation of the boarder between mesencephalon and rhombencephalon

A

FGF8

72
Q

_____ triggers the formation of another border within prosencephalon (Divides telencephalon and diencephalon)

A

Shh

73
Q

Formation of the neural tube by folding of the neural plate is called ____.

A

Primary neurulation

74
Q

The neural tube gives rise to the brain and spinal cord, EXCEPT

A

sacral and coccygeal levels

75
Q

4 general steps of primary neurulation

A

1) Elongation
2) Folding
3) Convergence
4) Closure

76
Q

Elongation

A

neural plate proliferates, neural cells grow bigger and elongate

neural plate bending at MHP (medial hingepoint) to form neural groove

77
Q

Folding

A

elevation of neural folds, approaches neural crest towards dorsal midline

folds form at day 18 (post feralization)

78
Q

Convergence

A

dorsolateral hinge points (DLHP)

allow neural folds to bend inward and converge at top

Day 20 PF

79
Q

Closure

A

neural folds fuse and neural crest delaminate

Closure points/points- regional differences in closure process

80
Q

Secondary neurulation: Caudal part of neural tube forms mass of ______ that acquired neural fate`

Secondary neural tube forms from ____ ___ by cavitation.

___ and ___ segments of spinal cord and vertebrae are formed by secondary neurulation.

A

mass mesenchyme progenitors

caudal eminence

sacral and coccygeal segments of spinal cord

81
Q

Secondary neurulation:

caudal neural tube underlain by the ________ and ____ more ventrally. During subsequent development in humans, caudal most tube undergoes dengeration by ____ with coccygeal segment last remaining.

A

tail notochord
tail-gut

apoptosis

82
Q

Caudal eminence (aka tail bud) derives from ____ ____.

During 6th week, caudal eminence (after primary tube is closed) ___, ____ and ___ with primary neural tube.

A

Enlarges

Cavitates

Fuses

83
Q

2ndary neurulation is stages

A

16-17

early development after closure and induction

84
Q

Closure of the neural tube at 2 main closure points

A

1: hindbrain cervical junction
3: forebrain junction

closes like a zipper
caudally from closure 3, rostrally and caudally from closure 1

85
Q

Anterior neuropore closes day ____

Posterior neuropore closes day ____

secondary neurulation proceed from the level of the closed ____ neuropore.

A

24 PF

26 PF

posterior neuropore

86
Q

The neural tube is covered by ____ which forms vertebral arches and skull.

Closure of vertebral arches is complete at ___ weeks gestation.

A

mesenchyme

11 weeks

87
Q

Mice vs. human closure points

A

mice have closure point 2, not in humans

mice initially have 3 neuropores

Convergence and zippering is slightly different, instruction signals different too.

88
Q

What is the important of closure points?

A

failure at different points to give rise to different phenotypes, some compatible with life, some not

89
Q

NTD are the ___ most common malformation.

Most due to ____ problems.
formerly 1/1,000, but

A

second

Closure

now decline with preventative measures

90
Q

Craniorachischisis

A

failure at closure 1

most serve NTD

combines open neural tube at midbrain, hindbrain, and entire spinal cord

91
Q

Anencephaly

A

closure 1 complete, but ZIPPERING TOWARD CRANIAL NEURAL TUBE is defective

92
Q

What is “split face” with anencephaly?

A

Rare form that happens due to failure of CLOSURE 3

93
Q

Can you survive with cranioachischisis and anencephalies?

A

No, incompatible with life.
Exposure of open neural tube to amniotic fluid environment leads to neuroepithelial degeneration (with massive neural tissue loss by end of pregnancy)

94
Q

Spinal bifida

A

failure of closure of POSTERIOR TUBE or at the POSTERIOR NEUROPORE (in spinal region) and lack of fusion of vertebral arches
soft tissue, and skin that cover back.

Upper limit of opening can appear at vary axial levels, depending on when progression of zippering became arrested.

Can live, but defects

95
Q

Closed SB (spina bifida occulta)

A

vertebral arches absent

hairy patch of skin over defect

spinal cord almost normal, but filum terminale (meningeal specialization at end of cord) may be tethered to subcutatneous tissue.

96
Q

Open SB

A

neural tissue from open neural plate lies on the dorsal surface of the fetus. Sometimes is contained in sac that protrudes through bone (myelomeningocele)

97
Q

Exencephaly

A

brain protrudes through a defect in cranial vault and is gradually destroyed due to mechanical injury/vascular disruption.

Due to FAILURE OF SKULL CLOSURE (derived from neural crest) not neural tube itself.

Rare to have exencephaly without anencephaly

98
Q

World wide reduction of ___ of NTDs.

A

50-70%

99
Q

Causes of NTD: polygenic and environment

A

200+ genes, 50x increase in general population

two polymorphisms of FOLATE DEPENDENT ENZYMES (5,10-methylenetetrahydofolate reductase)

MTHFR C677T
MTHFR A1298C

Environment: folate levels, overweight, teratogens

100
Q

How do you detect NTDs?

A

Blood test and imaging

Imaging detects earlier- week 10

101
Q

What are blood tests for NTDs looking for

A

alpha-fetoprotein (AF) and acetylcholinesterase

which leaks into amniotic fluid/maternal blood

102
Q

Preventative measures (protect against NTDs)

A

Folate fortification

reduced teratogen exposure

improve diet

103
Q

____ ____ in neuroepithelium = rapid division of progenitors and changes in shape/size critical for formation of medial and lateral hingepoints (MHP/DLHP)

A

Intrinsic changes

104
Q

At hinge points, NP cells become

A

taller, narrower, and re-arrange to align RC in row

only 1 layer at hinge

105
Q

Why is extrinsic influence from the ectorderm critical for elevation of neural folds?

A

EE cells (extrinsic ectodermal) produced LATERAL PUSH that elevates the folds

106
Q

What is folate required for?

A

dna (PURINE a/g) synthesis

remethylation of methionine

limiting factor in DNA/protein synthesis

107
Q

What signaling pathway produces an apical belt, reorganizes actin, and polarizes cells apical vs. basal, L/R.

Also reorients spindle fibers

A

PCP (Wnt non canonical signaling pathway)

108
Q

In mammels, ____ are required for medial hinge formation. What happens if they are mutated?

A

Vangl2 and Celsr1

medial hinge formation

109
Q

Vangl2 het + Grhl3 het (non PCP gene) causes ________

Vangl2 het: Cthrc1 het (Wnt canonical factors) causes ______

A

spinal bifida

exencephaly

110
Q

Shh activation promotes ___ factors to control PROLIFERATION AND FATE OF NEURAL PROGENITORS.

A

Gil factors

111
Q

Ptch1 mutation released SMO from inactivation and produce failure of ___________.

Gli2 mutations produces __________.

Mutations in Shh negative regulators produces either ____, ____ or both

A

Closure 1/craniorachischisis

exencephaly

spinal bifida, exencephaly

112
Q

shh signaling prevents BENDING AT DORSAL REGION by inhibiting ___

A

noggin

113
Q

Increase in shh:

decrease in shh:

A

increase; no DLHP and spina bifida

decrease: premature formation of DLHP and abnormal closure of tube

114
Q

What happens if RA synthesis enzyme, metabolism or receptors are damaged?

A

issues, it’s also tetraogens, we don’t get it

115
Q

Can inositol supplementation help NTD?

A

Yes, but we don’t know how. seems to do with PKC

116
Q

Holoprosencephaly (HPE): forebrain fails to

A

divide into two separate hemispheres and ventricles

most common birth defects in humans

no midline structures of the ventral forebrain

117
Q

HPE: total absence of interhemispheric fissure

A

alobar HPE

118
Q

HPE: partial separation of hemisphere

A

semilobar HPE

119
Q

HPE: separation of ventricles occurs, but the cortical structures are continuous

A

Lobar HPE

120
Q

HPE: accompanying facial abnormalities:

A

anophthalmia, cyclopia, single nostril, cleft lip/palate

121
Q

HPE problems:
___ signaling, issues patterning ventral midline structures.
____: TGF-beta, prechordal plate
__ and ___ transcription factors (in ventral neural tube)

A

Shh signaling

nodal

six3 and Zic2

122
Q

Cyclopia: optic field in neural plate is initially only ___ at midline that separates over time.

A

Patch

123
Q

Shh released from PCP patterns ventral midline

A

Six3- maintains shh

Shh –> + Pax 2 —| Pax 6

Pax6/six3 anterior neural plate

124
Q

mouse genes cause via disturbance of

A

1) cytoskeleton
2) cell proliferation and neuronal differentiation
3) neuroepithelial cell death
4) alteration of transcriptional regulation and chromatin dynamics
5) shh signals

Environment: low folate, diabetes, teratogenic, antiepileptic valproate

Neuroscience-special topic (8 decks)

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