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DEVELOPMENTAL > week 11 > Flashcards

week 11 Flashcards

1
Q

the anterior-posterior and dorso-ventral axes of Drosophila are specified in a _____

A

syncytium

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2
Q

transcription factors form _______

A

morphogen gradients

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3
Q

in many arthropods anterior-most segments form in a ___ but remaining segments form ____

A

syncytium

sequentially

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4
Q

in invertebrates AP and DV polarity is established in a _____

A

cellular environment

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5
Q

in vertebrates the determination of axes occurs partially in ____

A

a cellular environment

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6
Q

Asymmetry is already established in the oocyte (egg), what are the 2 poles?

A

animal pole - dark - contains nucleus

vegetal pole - white

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7
Q

The first cleavage in a vertebrate embryo is parrallel with ____

A

animal - vegetal axis

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8
Q

Animal-vegetal axis broadly defines the anterior / posterior axis. What showed this? and what is it?

A

fate map studies

animal is anterior and vegetal is posteror

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9
Q

The oocyte contains cytoplasmic determinants. What are these?

A

these are maternal mRNAs and proteins deposited in the egg before fertilisation

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10
Q

Why are cytoplasmic determinants important?

A

because it is enough material to see the embryo through the first cleavages until its own genes begin to be expressed

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11
Q

where do most of the developmentally important maternal products end up?

A

in the vegetal hemisphere

the yolk

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12
Q

What does removal of the vegetal half of the embryo affect?

A

AP and DV polarity

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13
Q

Experiment by Oppenheimer 1936 showed what?

A

fish

remove yolk early you get a radially symmetrical hyperblastula with no AP or DV pattern

remove yolk later it is a normal embryo

remove only the most vegetal yolk there is some AP and DV character

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14
Q

What does the experiment by Oppenheimer indicate?

A

that a diffusible molecule in the yolk is required to pattern the embryo.

Signal removed with yolk there is no positional information. Small amount of signal remains there is a limited gradient and hence limited positional information. Gradient established key positional information is already given and hence can remove yolk late on.

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15
Q

What was Spemanns experiment in 1903?

A

ligature along the plane of first division in normal embryos.
Released the ligation so that one nucleus could move over and you get 2 normal embryos. so every single nuclei is capable of generating a complete salamander

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16
Q

The outcome of the ligature experiment?

A

Depends on the cytoplasmic regions included in each blastomere

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17
Q

what is the gray crescent?

A

after fertilisation it appears

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18
Q

why is the gray crescent important?

A

the part of that receives the grey crescent after ligature develops normally

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19
Q

What is the function of the grey crescent??

A

contains the blastopore lip
and the formation of a secondary axis occurs after dorsal lip tissue transplantation

the transplant induces host tissue to form a secondary embryo

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20
Q

the dorsal blastopore lip is known as ____

A

Spemann organiser

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21
Q

how does the spemman organiser fomr?

A

the endoderm secretes the protein Vg1 and induces the mesoderm

the dorsal most endoderm cells induce the Spemann organizer - the Nieuwkoop center

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22
Q

the mesodermal cells receive different signals why?

A

because the mesodermal cells have different fates depending on their position along the DV axis

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23
Q

what is the Niewkoop center?

A

it is the dorsalmost vegetal cells in the endoderm which signal for the Spemann organiser to form

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24
Q

What gives the cells of the Nieuwkoop center their special properties?

A

beta catenin

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25
Q

beta catenin accumulates where in the embryo?

A

in the nuclei on the dorsal side after fertilisation

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26
Q

what does injecting beta catenin do?

A

in the ventral side where it is not normally causes a secondary axis to be produced

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27
Q

which mechanisms are involved in localising beta catenin?

A

Wnt signalling

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28
Q

Explain the Wnt signalling pathway

A

in the absence of Wnt signalling beta catenin is degraded

if Wnt binds, Disheveled is activated by Frizzled

Dsh together with GBP inhibits GSK3 from binding beta catenin

beta catenin is freed and can enter the nucleus

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29
Q

What happens to Disheveled and GBP during cortical rotation? How?

A

re located

Dsh and GBP associate with kinesin at the vegetal pole of the unfertilised egg. After fertilisation these proteins are translocated dorsally via subcortical microtubule tracts.

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30
Q

the dorsal side forms where?

A

always opposite the sperm entry site

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31
Q

How is there dorsal enrichment of Dsh and GBP and inhibition of GSK3?

A

Dsh and GBP are released from kinesin and accumulate in future dorsal third of 1-cell embryo.
Dsh and GBP block GSK3. Beta catenin is not degraded on the dorsal side

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32
Q

What is the consequence of beta catenin localisation to the nucleus on the dorsal side of the embryo?

A

results in the induction of the organiser

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33
Q

A beta catenin /____ complex binds to the siamois and twin promoters

A

Tcf3

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34
Q

Tcf3 on its own ____ the expression of siamois and twin genes

A

represses

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35
Q

Tcf3 binding to siamois and twin promoters causes the activation of _____ a gene that is expressed in the _________

A

goosecoid

spemann organiser

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36
Q

What is the role of the organiser protein Goosecoid? (5)

A

activates the migration properties of the dorsal blastopore lip

autonomously determines the dorsal mesodermal fates of those cells expressing it

enables cells to recruit neighbouring cells into the dorsal axis

activates genes for brain formation in neighbouring tissues (mesoderm and ectoderm)

represses ventralising genes e.g. Wnt8

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37
Q

The organiser establishes a nodal gradient, explain

A

higher levels of beta catenin activate more nodal related genes than do lower concentrations

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38
Q

Nodal abbreviation

A

Xnr

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39
Q

beta catenin and which 2 proteins activate Xnr?

A

VegT and Vg1

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40
Q

Xnr is highest where?

A

in the dorsal region

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41
Q

The Xnr gradient specifies what?

A

The various mesodermal fates

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42
Q

what are BMPs?

A

bone morphogenetic proteins

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43
Q

what do BMPs do?

A

they are antagonists of the organiser

44
Q

BMP4 is highest where?

A

in the ventral region

45
Q

BMP gradient ___ to ___

Nodal gradient __ to ___

A

ventral to dorsal (high low)

dorsal to ventral (high low)

46
Q

BMP signalling leads to what?

A

the expression of different genes at different concentrations

47
Q

what does BMP activity pattern?

A

the mesoderm along the DV axis

48
Q

BMP is expressed where?

A

throughout the marginal zone except the organiser

49
Q

What inhibits BMP in the organiser?

A

Noggin and Chordin diffuse out to inhibit BMP binding to its receptor

50
Q

most dorsal (high Nodal, high Chordin) makes ___ and ___

A

organiser

notochord

51
Q

most ventral (low Nodal, low Chordin) makes __ and ___

A

blood

gut endoderm

52
Q

How do planarians reproduce?

A

sexually

asexually - regeneration

53
Q

What do planarians do in unfavourable environments?

A

shrink

54
Q

how many days does it take for a planarian to regenerate?

A

17 days

55
Q

Planarians have a population of ____ that can regenerate all tissues

A

neoblasts - they are pluripotent

56
Q

What are involved in the development and regeneration of planarians?

A

morphogen gradients

57
Q

The rate of head generation decreases towards ___

A

posterior

58
Q

what is the main morphogen in control of planarian regeneration?

A

Wnt/ beta catenin gradient

59
Q

what happens when beta catenin1 RNAi is injected into planarians?

A

if the levels of beta catenine are lowered then odd phenotypes are produced. See graphs.

high conc. of beta catenin = tail
low conc. of beta catenin = head

60
Q

What is the polar coordinate model?

A

cells receive positional information along the anterior-posterior and dorso-ventral axes

61
Q

how do you test the polar co-ordinate model?

A

cut a piece out and rotate it

62
Q

define morphogen

A

a protein that works concentration dependent, it has to be there at a specific concentration, it does different things at different concentrations

63
Q

the dorsal lip of the blastopore is _______ in the amphibian embryo

A

site of initiation of gastrulation

64
Q

which 2 morphogens determine the fate of dorsal ventral? How?

A

BMP and Nodal
BMP is higher in the ventral
Nodal is higher in the dorsal

65
Q

when you take a small slice of a planarian you get 2 heads instead of 2 complete planarians, why?

A

the morphogen gradient. need a certain size of tissue to have a proper gradient, so if the slice is too thin then that wont work because there is not a proper gradient due to size. Length to width proportions

66
Q

In a planarian when you remove the head and then cut out a slice you get a 2 headed planarian why?

A

the information is missing so these cells dont have neighbouring cells and each of them will form a head they dont recognise there are other cells so they dont have the proper positional information

67
Q

define regeneration

A

the reactivation of development in post embryonic life to restore missing tissue

68
Q

what are the 4 methods of regeneration?

A

stem cell mediated regeneration
epimorphosis
morphallaxis
compensatory rengeneration

69
Q

define stem cell mediated regeneration

A

stem cell can proliferate creating more stem cells (self renewal) e.g. regrowth of hair, replacement of blood cells

70
Q

define epimorphosis

A

dedifferentiation of adult structures to form an undifferentiated mass of cells that then become respecified
e.g. regeneration of salamander limbs

71
Q

define morphallaxis

A

regeneration occurs through repatterning of existing tissue with little new growth

72
Q

define compensatory regeneration

A

differentiated cells divide but maintain their differentiated functions

73
Q

how does a stem cell give rise to more differentiated cellular progeny?

A

by asymmetric cell divisions

74
Q

what are adult stem cells?

A

populations of embryonic stem cells which have been retained

75
Q

Hematopoetic stem cells are derived from 3 embryonic regions?

A

Placenta
Yolk sac
Aorta gonad mesonephros

76
Q

____ form the stem cell niche by which the hematopoetic stem cell population is maintained throughout life

A

osteoblasts

77
Q

Osteoblasts signal to the hematopoetic stem cells by activating 3 signal transduction pathways?

A

notch
Wnt
Receptor tyrosine kinase

78
Q

_____ cause HSCs to differentiate along a particular pathway

A

cytokines

79
Q

what is the cancer stem cell hypothesis?

A

certain cancers arise from adult stem cells.
Human myeloid leukemias and astrocytic brain tumours have both been linked to stem cells that have managed to enter new domains and retain their stem cell properties

80
Q

what can the cancer stem cell knowledge be used for?

A

to cure cancer - differentiation therapy

81
Q

how would differentiation therapy work?

A

if the cancerous cell is actually a stem cell then it might be controlled by the right mixture of paracrine factors

82
Q

what was found from using differentiation therapy?

A

it was found that acute promyelocytic leukemia which causes neutrophils to become malignant can be cured by retinoic acid as it is able to induce the differnetiation of the leukemic cells into normal neutrophils

83
Q

Epimorphic generation of salamander limbs, explain

A

after amputation epidermal cells move to wound and form the apical ectodermal cap.

Cells dedifferentiate and form a proliferating mass of cells beneath the cap which is called blastema

84
Q

How do cells regain the ability to divide?

A

thrombin
a protease
is released when the amputation occurs

85
Q

what happens when Thrombin comes into contact with blood serum?

A

an unknown factor is produced which causes differentiated cells to enter the cell cycle and dedifferentiate

86
Q

___ are required for blastema cells to proliferate

A

nerves

87
Q

A minimum number of nerve fibres must be present for regeneration to take place. ______ is in addition required for angiogenesis and pattern formation

A

fibroblast growth factor 2

88
Q

Fibroblast growth factor 10 is also required for the proliferation of the blastema cells. What happens when beads of this are placed in the stump of a frog hind limb?

A

the hind limb will regenerate

89
Q

Morphallic regeneration occurs in ___

A

hydra

90
Q

Hydra does not show senescence it is an immortal organism. Explain

A

the cells in the body column proliferate and are continuously displaced towards the hypostome and the foot. the cells differentiate in response to positional information in the body column as they migrate and finally slough off.

91
Q

if hydra is cut into pieces each piece will regenerate a complete hydra. recent publications show that _____ are involved in head regeneration

A

stem cells

92
Q

Explain compensatory regeneration in the mammalian liver

A

the injury of the liver is sensed through the blood stream by Kupfer and Stellate cells. These cells secrete tumour necrosis factor alpha and hepatocyte growth factor among others. this leads to the activation of cyclin D and E and cell division in the hepatocyte. the 5 types of liver cells do not dedifferentiate but produce more of themselves

93
Q

The CNS of adult birds and mammals is not capable of regeneration but the CNS can functionally compensate for injury, this can occur in 3 ways?

A

restitution
substitution
compensation

94
Q

what is restitution?

A

depends on the outgrowth of axons and dendrites from undamaged area and form new synapses within the damaged system to replace those lost to injury or cell death

95
Q

what is substitution?

A

involves the adoption of function by a related system that imperfectly repalces the failed or damaged system. Substitution is never complete

96
Q

what is compensation

A

involves the recovery of function due to adaptation of the undamaged components of the normal system so as to minimise the effects of a partial loss of function

97
Q

Therapeutic approaches to CNS injury use all 3 mechanisms, what are 2 examples?

A

rehabilitative medicine works to enhance the efficacy of any residual function using physical training.

pharmacological agents can increase the conduction velocity of axons and therefore support the functional compensation

98
Q

Peripheral axons of mature nerves are surrounded by three layers of connective tissue?

A

epineurium
perineurium
endoneurium

99
Q

what is the epineurium?

A

consists of fibroblasts, fat cells, small blood vessels and collagenous matrix, surrounds the entire nerve

100
Q

what is the perineurium?

A

consists of a collagen matrix and specialised cells that form the blood brain barrier, surrounds individual nerve fascicles

101
Q

what is the endoneurium

A

consists of a collagen layer, surrounds individual axons

102
Q

The ability of the peripheral nerves to regenerate depends on the _____

A

severity of the injury

103
Q

what is the process of regeneration in the CNS?

A

injury
inflammation, activation of Schwann cells
Sprouting
Traverse region of injury, navigate back to original target
Reestablish synaptic contact, remyelination

104
Q

Activated Schwann cells (PNS glia) produce a highly growth promoting environment. Explain

A

these factors stimulate the axons to regenerate. If the injury is mild and the Schwann cells can fill the gap between the distal and proximal nerve, there is a good chance that the nerve will regenerate

105
Q

what is thought about the glial scar?

A

it may present a physical barrier that can not be penetrated by axons. the ECM of the glial scar expresses a large number of highly interactive molecules that are crosslinked

the high density of the glial cells in the glial scar might also act as physical barrier. Neurotrophic factors expressed in the scar not only promote neural growth but also glial growth, therefore they might contribute to the density.

106
Q

What could prevent axon outgrowth

A

high concentrations of cell adhesion molecules might prevent axon outgrowth

cell migration can only occur over a narrow range of matrix concentrations where cells adhere strongly enough to generate traction, without being so strongly adhered that they are unable to change position. It can be assumed that the same is true for axons. They have to attach, detach and re-attach in order to move along a substrate. Therefore, high concentrations of cell adhesion molecules in the glial scar could prevent axon outgrowth

107
Q

3 reasons why CNS regeneration fails?

A

substrate: wrong concentration of CAMs

Axons: wrong receptors

Physical barrier - glial scar

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