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ARD Year 1 > Development > Flashcards

Development Flashcards

1
Q

Primordial germ cells are what? Haploid or Diploid?

A

Diploid

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2
Q

When does the egg complete its first meiosis?

A

At ovulation

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3
Q

Entry of sperm into the oocyte leads to the formation of the earliest embryo which is known as a what?

A

Zygote

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4
Q

What is distinguishing about the head of bovine sperm?

A

Has a spike upon it

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5
Q

What is the surface of the oocyte better known as?

A

Zona Pellucida

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6
Q

Sperm entry causes the zona pellucida to become impenetrable, why is this important?

A 
Prevents polysperming
(Usually do not get past more than a few divisions)
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7
Q

Sperm entry causes the oocyte to undergo what in order to attain a haploid chromosome number?

A

2nd meiosis

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8
Q

How is the diploid number attained in the zygotic stage?

A

Diploid (2N) = 1N from sperm + 1N from egg

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9
Q

What is initiated at the zygotic stage?

A

Cell division

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10
Q

What are cells called at the cleavage stage and how many are there?

A

Blastomeres - 4

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11
Q

How many blastomeres are in contact with the zona pellucida at the cleavage stage?

A

All - 4

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12
Q

At the cleavage stage, in mammals, what type of cell division is occurring?

A

Asynchronous

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13
Q

The 16 cell stage is also known as the what?

A

Morula Stage

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14
Q

While cells divide in the morula stage, what is conserved? How is this done?

A

Embryo size - cells divide but do not grow

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15
Q

Continued cell division makes some cells become located on the inside of the ball of cells, what are these better known as?

A

The inner cell mass (ICM)

No longer in contact with zona pellucida

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16
Q

The first differentiation event occurs in which embryonic stage?

A

Blastocyst Stage

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17
Q

How is the blastocyst cavity formed?

A

Cells on the outside pump fluid into the embryo

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18
Q

After the inner cell mass has condensed, what are the outside cells called?

A

Trophoblasts

Supporting tissue for the embryo

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19
Q

During the blastocyst stage what involving the zona pellucida occurs?

A

The blastocyst hatches from the zona pellucida which is digested by enzymes, the embryo will be lost if this does not occur

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20
Q

Where should implantation occur?

A

Outside of the oviduct within in the uterus

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21
Q

What percentage of ectopic pregnancies occur within the oviduct and what other locations can this occur?

A

> 90% and cervix

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22
Q

What is one cause of the high prevalence of ectopic pregnancy within the oviduct?

A

Oviduct narrowing due to infection which impedes movement

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23
Q

What are the complications caused by oviduct ectopic pregnancy?

A

Rupturing of oviduct, resulting in death of embryo (usually) and massive haemorrhaging, it is life threatening for mother and usually requires surgery

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24
Q

Once the trophoblast come in contact with the uterine wall, what are they induced to do?

A

Cells induced to divide and start to invade the endometrium

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25
Q

What becomes of invading trophoblast cells and those that do not?

A

Invading - loose their cell membrane and become multi-nuclear-synctiotrophoblasts and form a sheet like structure
Non-invading - retain membranes and called cytotrophoblasts

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26
Q

Once embryo becomes buried within the endometrium the inner cell mass forms two layers, what are these and where are they found?

A

Epiblast-columnar cells - adjacent to syncytiotrophoblast cells
Hypoblast-cuboidal cells - facing the blastocyst cavity (yolk sac)

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27
Q

Which cells are more totipotent, inner cell mass cells or trophoblast cells and why? What cells can these differentiate into?

A

ICM is more totipotent as can differentiate into all cell types other than placenta while the trophoblasts can only differentiate into placental cells

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28
Q

What do the epiblast and hypoblast cells form? What does these structures form within the adult?

A

Epiblast - Ectoderm (Dif. into all neural tissues), Mesoderm (Dif. into muscle, bones, organs etc.) and Endoderm (Dif. into lining of gut and derivatives)
Hypoblast - Supporting membranes and forms no adult tissue

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29
Q

Majority of animals are bilateria, therefore they all have what?

A

3 germ layers
Mirror image symmetry
Two defined axis at right angles to each other (dorsal-ventral and anterior-posterior)

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30
Q

How many germ layers do jellyfish and sponges have?

A

2

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31
Q

What is promoted by an animal being bilateral?

A

Formation of a head and central nervous system - necessary to help animals coordinate movement and become successful predators

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32
Q

In drosophila, the anterior and posterior ends are defined by the expression of two maternal genes each, what are these genes that are translated into protein that act as transcription factors?

A

Anterior - bicoid and hunchback genes

Posterior - nonos and caudal genes

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33
Q

What are morphogens?

A

Molecules that tell the cells within the embryo what to do, they have one function at high concentrations and one function at low concentrations, these gradients appear throughout the embryo

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34
Q

In the mouse and drosophila, when is the anterior-posterior axis established, before or after fertilisation?

A

Mouse - after fertilisation

Drosophila - before fertilisation

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35
Q

In drosophila, during the formation of the dorsal-ventral axis, the transcription factor Dorsal move into the nucleus of which side only?

A

Ventral

Activates and suppresses transcription of specific genes

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36
Q

In xenopus, the dorsal-ventral axis is established rapidly after fertilisation, what is the maternal effect gene that is restricted within the oocyte and moves following fertilisation? Where does this factor move to following fertilisation?

A

Dishevelled (dsh) and following fertilisation, dsh moves to the dorsal side of the oocyte

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37
Q

What effect does Dishevelled have on what enzyme that normally breaks down beta-catenin?

A

dsh inhibits the enzyme activity of GSK3beta, which normally breaks down beta-catenin
(therefore, dsh on dorsal side results in increased beta-catenin on the dorsal side)

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38
Q

When beta-catenin moves into the nucleus on the dorsal side of the xenopus embryo, it activates the expression of which gene?

A

Siamois

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39
Q

In xenopus, if beta-catenin builds up on both the dorsal and ventral side of the embryo what occurs?

A

a double dorsal forms resulting in two heads and no gut

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40
Q

In drosophila, what are the four different groups of segmentation genes, what order are they expressed and what do they do in the drosophila embryo?

A

First - Gap genes - divide embryo into four broad domains
Second - Pair-rule genes - divide into the fourteen subunits
Third - Segment polarity genes - divides each subunit into anterior and posterior domains
Forth - homeotic selector genes - determines the fate of each segment

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41
Q

Are gap genes maternal or zygotic?

A

zygotic - produced by embryo

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42
Q

Name 3 of the 5 transcription factors encoded by gap genes in the drosophila

A

Hunchback, Giant, Kruppel, Knirps, Tailless

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43
Q

What genes control the expression of gap genes?

A

Maternal Effect Genes

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44
Q

Name four transcription factor encoded by pair rule genes?

A

Hairy, even-skipped, runt, fushi tarazu, odd-skipped and paired

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45
Q

how many segments do pair-rule genes split the drosophila embryo into?

A

14

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46
Q

What controls the expression of pair-rule genes?

A

Gap genes

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47
Q

Segment polarity genes consist mainly of signalling molecules, name two examples?

A

hedgehog and Wingless

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48
Q

What is the function of segment polarity genes and what controls their expression?

A

Divide each segment of drosophila embryo into an anterior and posterior region - expression controlled by pair-rule genes and then mutual repression

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49
Q

In the drosophila embryo after expression of segment polarity genes, the signalling molecule hedgehog is found in which region of the individual segments?

A

Anterior

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50
Q

Define the process of homeosis?

A

Transformation of a whole segment or structure into a related one

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51
Q

What are the homeotic complex (Hom-C0) also known as?

A

Hox genes

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52
Q

What does the deletion of the Hoxc* in the mouse do in relation to the patterning along the anterior-posterior axis?

A

Transforms the first lumbar vertebrae into one of thoracic characteristics (homeotic transformation)

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53
Q

What effects does the knockout of Hox10aaccdd and Hox11aaccdd have on the anterior-posterior patterning in mice?

A

Hox10aaccdd - Lumbar converted to Thoracic

Hox11aaccdd - Sacral converted to Lumbar

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54
Q

What genes dictate the type of vertebrae formed along the anterior-posterior axis?

A

Hox genes

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55
Q

Which types of vertebrae i.e. anterior (cervical + thoracic) and posterior (lumbar, caudal + sacral) are more coded by Hox genes?

A

Anterior

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56
Q

What are the adult derivatives of somites?

A

Axial skeleton, vertebrae, ribs, skeletal muscle: body and limb, dermis

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57
Q

From what are somites formed from? Intermediate mesoderm, Midline mesoderm, Paraxial mesoderm or Lateral plate mesoderm?

A

Paraxial mesoderm

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58
Q

Name the two derivatives of somites and the subsequent derivatives from these two products?

A

Sclerotome : Axial skeleton, ribs and vertebrae

Dermomyotome : dermatome (dermis), myotome (skeletal muscle: body and limb)

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59
Q

What effect does temperature have on cell division of the presomitic mesoderm?

A

Affects the frequency of generation of somites, but the final somite number remains constant

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60
Q

Is environment important in somitogenesis and what evidence is there to support this?

A

No, isolated presomitic mesoderm in culture still develops somites so the environment is not important

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61
Q

Is the number of cells in the presomitic mesoderm important? what evidence is there to support this?

A

No, if remove a slice of presomitic mesoderm, somites still form at a normal rate - only smaller in size

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62
Q

How are somites formed at regular intervals?

A

Hairy is expressed in periodic intervals corresponding to the appearance of a new somite
Each cell expresses hairy 12 times as it moves towards the anterior presomitic mesoderm, after which it forms part of a somite

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63
Q

How are the boundaries between somites defined?

A

Fgf8 is expressed in cells in and around the node, as these cells move in a rostral direction during gastrulation, the Fgf8 mRNA is degraded creating a gradient: low Fgf8, rostral and high Fgf8, caudal
At a specific threshold level, somite formation occurs. This results in the successive definition of where a somite starts to form in the presomitic mesoderm

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64
Q

Describe the state of somites I to III?

A

the somite is an epithelial ball surrounding cells that remain mesenchymal, called somitocoel cells

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65
Q

What portion of the somites become sclerotome and how does this occur?

A

The ventral-medial portion of somites undergo epithelial-mesenchymal transition and becomes sclerotome
The somitocoel cells join the mesenchymal cells and also become part of the sclerotome

66
Q

The limb bud mesenchyme induces what morphological change in the distal limb ectoderm resulting in the formation of what?

A

A localised thickening (cuboidal to columnar shape cells)

Forms the apical ectodermal ridge

67
Q

What is the result of removing the AER? What does this tell us?

A

truncation - the severity of which is dependent on time of AER removal
Tells us:
The AER regulates proximal-distal outgrowth
proximal tissues are laid down first

68
Q

What factors can be substituted for the AER? How was this shown and what does this tell us?

A

FGFs - in ectopic places, it can induce ectopic limbs

Tells us Fgfs induce limb development and outgrowth

69
Q

Does the AER control proximal-distal patterning? What evidence is there to support this?

A

No - Transplantation of differing age AER gives normal limb showing the AER only controls outgrowth

70
Q

What is the progress zone in relation to the AER?

A

A population of rapidly dividing mesenchymal cells immediately below the AER
It is of finite size and cells within cannot differentiate until they leave it

71
Q

How does the progress zone control limb proximal-distal patterning?

A

Rapid cell division in the PZ leads to other cells having to leave it, the first cells to lave differentiate to have a proximal identity while the last cells to leave differentiate to have a distal identity
The time cells spend in PZ reflects their identity

72
Q

What effect does removal of the AER have on the progress zone?

A

Leads to elimination of PZ by cell death
The cells that have left PZ at AER removal are not affected and the differentiate resulting in truncation, explaining phenotype seen when AER removed

73
Q

What occurs when a young PZ is grafted onto an older limb bud and vice versa?

A

Young PZ on Old bud = duplicated ulna and radius

Old PZ and Young bud = lack of intermediate structures

74
Q

What genes control proximal-distal patterning of the limb?

A

Hox A genes pattern the PD axis, the longer a cell is in the PZ, the more Hox genes it expresses
The Hox A genes expressed determine whether that cell is part of the stylopod, zeugopod or autopod

75
Q

Where is anterior-posterior patterning seen in limb formation?

A

Formation of digits

76
Q

What is polydactyly

A

Congenital physical abnormality results in more than five fingers and is common in animals and humans

77
Q

What is the zone of polarising activity and where is it found in limb development?

A

posterior distal limb mesenchyme and is always located at the posterior distal position and always located adjacent to the AER

78
Q

What is the result of transplantation of the zone of polarising activity to the anterior of the limb bud

A

Produces extra digits, these extra digits develop as mirror image of normal
Transplantation of a few cells give only anterior digits with more cells gives posterior and anterior digits
Means the ZPA works in dose dependent manner to specify posterior fates

79
Q

What are the mechanisms of ZPA activity?

A

ZPA cells themselves do not form digits
They produce a diffusible compound (morphogen) whose effect is concentration dependent
ZPA activity can be mimicked by sonic hedgehog
ZPA patterns a field of mesenchymal cells
Hox D gene expression determines anterior-posterior identity while Hox A gene expression determines proximal-distal identity

80
Q

What internal and external structures does dorsal-ventral patterning control? what germ layers does it therefore control?

A

External - hair, nails, footpads etc.
Internal - muscle, bones etc.
Therefore controls the ectoderm and mesoderm

81
Q

Wheres does the dorsal-ventral patterning information reside? what evidence is there to support this?

A

DV patterning is controlled by the ectoderm

Evidence - if you rotate the ectoderm 180 degrees the DV patterning is also rotated 180

82
Q

What effect does the ectoderm have on the mesoderm in relation to DV patterning?

A

Dorsal ectoderm patterns the underlying mesoderm to become dorsal mesoderm
Ventral ectoderm patterns the underlying mesoderm to become ventral mesoderm

83
Q

What is the effect of a loss of dorsal or ventral ectoderm identity on AER and what does this tell us?

A

If there a loss, the AER does not form in the correct place, this tells us that DV patterning also controls the positioning of the AER
The AER is positioned at the boundary between the dorsal and ventral ectoderm

84
Q

What is the dorsal signal of dorsal-ventral patterning?

A

Wnt7a

85
Q

What controls proximal-distal outgrowth, anterior-posterior patterning and dorsal-ventral patterning?

A

PD outgrowth - controlled by AER (FGFs)
AP patterning - controlled by the ZPA (Shh)
DV patterning - controlled by ectoderm (Wnt7a is dorsal factor)

86
Q

What evidence is there to support this statement - Devlopment of all three axis must be coordinated. each signalling centre not only patterns tissue but regulates activity of other signalling centres?

A

AER removal leads to loss of ZPA
Loss of ZPA leads to loss of AER
Loss of dorsal ectoderm signal leads to loss of AER and therefore ZPA

87
Q

Name two examples of intergration of signalling cascades in limb development

A

Establishment of ZPA (Shh) by AER (Fgf8) and dHAND
Induction of Fgfs (AER) by Shh (ZPA)
Shh maintainance (ZPA) by Wnt7a (dorsal ectoderm)
Determination of AER size by Wnt7a

88
Q

Which is the most correct statement about progress zone:

a) it is in the ectoderm
b) it resides under the apical ectodermal ridge
c) the whole of it expresses Shh
d) it is derived from paraxial mesoderm

A

B

89
Q

What would you hypothesise would be the result of removing Fgf10 during limb development:

a) mirror image digits
b) no stylopod
c) limbs develop in the wrong places
d) no signs of limb development

A

D

90
Q

What is the formula for generation of energy?

A

C6H12O6 + 6O2 –> 6CO2 + 6H20 + Energy

91
Q

Give an example of a simple organisms gaseous exchange system where the organisms does not need gills/lungs?

A

Hydra - gases diffuse into and out of cells directly down a concentration gradient
Insects - air can diffuse directly from tracheoles into the cells of the body
These processes rely entirely upon diffusion, therefore the size of the organism is limited by the range of efficient diffusion of gases

92
Q

What are the several different classes of vessels which compose the circulatory system?

A

arteries and veins, arterioles and venules, capillaries

93
Q

Name an amphibian that possesses no gills or lungs and instead use skin for gas exchange

A

Some salamanders

94
Q

The endoderm forms the epithelium of the trachea and differentiates into three cell types which are?

A

Ciliated - clearance currents, moves mucus to larynx
Goblet - secrete mucus, traps particles
Clara - produces surfactant, keeps mucus fluid

95
Q

Imperfect rings provide support for the trachea, what is the origin of these rings?

A

Some mesoderm differentiates into cartilage which forms the rings

96
Q

What are the two types of alveolar cells?

A

Alveolar cells - very thin, gas exchange

Secretory cells - produce surfactant

97
Q

When does the respiratory diverticulum appear in humans?

A

At approximately 4 weeks

98
Q

What is the respiratory diverticulum?

A

A buc that evaginates from the ventral wall of the foregut - it is therefore endodermal in origin (like gut)

99
Q

Developing lung structures are surrounded by what?

A

Pleural mesenchyme

100
Q

What is the pleural mesenchyme?

A

A part of the splanchnic mesoderm that gives rise to the cartilage, muscle and connective tissue components of the trachea

101
Q

What signalling is required for lung induction?

A

FGFs

102
Q

What is pleural mesenchyme necessary for and what evidence is there to support this?

A

The pleural mesenchyme surrounding the epithelial lung bud is essential for growth and branching
Removal of the mesenchyme results in no growth

103
Q

One of the key roles of the pleural mesenchyme during outgrowth is to provide growth factors for the lung epithelium, give an example of one such factor

A

FGF 10

However signalling from the epithelium to the lung mesenchyme is also required during morphogenesis

104
Q

Differentiation of the different epithelial cell types is regulated by expression of different transcription factors, what are these factors for Goblet, Basal, Clara and Ciliated cells?`

A

Goblet - Spdef
Basal - p63
Clara - Ttf-1 and Foza1/a2
Ciliated - Foxj1, Foxa1/a2, Sox17 and Sox2

105
Q

When do the terminal sacs with cuboidal epithelium mature to produce alveoli with thin squamous epithelia?

A

Only during late foetal life and postnatal growth

Only a small fraction (up to 20%) of all alveoli are produced prior to birth

106
Q

What are the syndromes and lung malformations for the mutations of Shh/Gli, DHCR7, FGFR, Hox-b5, Nkx2.1, Cilia Proteins, SFTPB, SFTPC and ABCA3?

A

Shh/Gli - Pallister-Hall, ACTERL - tracheoesophageal fistula, tracheal malformations
DHCR7 - Smith Lemli Opitz - pulmonary hypoplasia
FGFR - Apert, Pfeiffer, Crouzon, Carpenter - tracheal cartilage abnormalities, pulmonary hyperplasia
Hox-b5 - unknown - bronchopulmonary sequestration
Nkx2.1 - Pulmonary hypoplasia/dysplasia - tracheoesophageal fistula
Cilia Proteins - Primary cilia dyskinesia
SFTPB, SFTPC and ABCA3 - Hereditary SP-B deficiency, SP-C mutations, ABCA3 transporter - respiratory distress/ pulmonary fibrosis

107
Q

What is the prevalence of Esophageal atresia and Tracheoesophageal fistula?

A

1 in 3000-5000 births

108
Q

A failure to completely septate the trachea from the oesophagus can be a result of abnormal what signalling? Give 2 examples

A

Shh, Nkx2.1, Tbx4, Foxf1 or Retinoic acid

109
Q

When are the cells of the primary heart field specified?

A

During gastrulation

110
Q

What cardiac marker do cells in the primary heart field express?

A

Cardiac marker Nkx2.5

111
Q

How is the heart tube formed during cardiac development?

A

Cardiac precursor cells differentiate and the two sides of the heart zip together to form the heart tube

112
Q

What does the heart tube consist of?

A

Primitive inflow tract (sinus venous), atrium, ventricle and outflow tract
This structure is very similar to the fish heart

113
Q

What happens following the formation of the heart tube to lead to the formation of a four chambered heart?

A

Straight heart tube is remodelled, the atrium is divided in two to give a three chambered structure - two atria one ventricle, common outflow tract (structure very similar to the frog heart)
Finally the left and right ventricles and the aortic and pulmonary circulations are divided (this gives the final adult four chambered heart structure)

114
Q

Division of the atria, ventricles and outflow tract is dependent upon four key events, what are they?

A

Septation of the atria, septation of the ventricles, septation of the outflow tract and alignment of the atria with the appropriate ventricle (right to right, left to left)

115
Q

The process of alignment of the atria with the ventricles is dependent upon the formation of endocardial cushions, what are it’s origins, derivatives and what does it do?

A

Origins - initially acellular but become populated by mesenchymal cells derived from the endocardium
Derivatives - give rise to valve tissue in the embryonic heart
What it does - fuse to produce the left and right AV canals

116
Q

What are the two different septa responsible for dividing the left and right atria?

A

Septum primum and septum secondum

117
Q

Explain the process of dividing the left and right atria

A

Septum primum grows down to separate atria leaving a gap at bottom called the ostium primum, which allows communication between the two atria
Ostium primum closes and a new gap in the centre of the septum primum called the ostium secondum forms, therefore the communication is maintained
Next the septum secondum grows down and covers the ostium secondum but still allows the communication between the atria

118
Q

The outflow tract contains endocardial cushions that develop in the same way as those in the AV canal, but these are not responsible for the septation of the OFT into aortic and pulmonary trunks, what is?

A

Neural crest cells

119
Q

Atrial septal defects are common, name two examples of these

A

1) septum primum does not grow down to AV cushion (persistent ostium primum)
2) septum secundum does no grow down far enough to cover the ostium secundum

120
Q

What causes the separation of the two ventricles?

A

The growth of a muscular septum

121
Q

Ventricular septal defects can be either muscular or membranous, define each?

A

Muscular - muscular part of the septum does not grow properly
Membranous - mesenchymal cap of the septum does not fuse with the AV cushion

122
Q

malformations can also arise from a failure of the neural crest to migrate, these cover a wide spectrum, give two examples

A

1) total acsence of the aorticopulmonary septum (common arterial trunk or persistant truncus arteriosus)
2) mis-positioning mutations (double outlet right ventricle, transposition of the great arteries)

123
Q

What are the three major shunts and openings the foetus develops to restrict blood flow to the liver and the lungs?

A

Ductus Venosus
Ductus Arteriosus
Foramen Ovale (ostium secundum)

124
Q

What is the ductus venosus?

A

foetal blood vessel connecting the umbilical vein to the inferior vena cava

125
Q

What is the purpose of the ductus venosus?

A

Causes half of the blood flow from the umbilical vein to be diverted into the inferior vena cava bypassing the liver while the other half passes through the liver and enter the IVC through the hepatic veins.

126
Q

How is blood flow through the ductus venosus regulated?

A

Blood flow regulated by a sphincter mechanism. sphincter closes - blood cannt flow into ductus venosus and therefore goes into the liver

127
Q

What is the function of the foramen ovale?

A

To protect the developing lung
Blood enters the right atrium at high pressure since comes directly from umbilical vein and has mostly bypassed the apillary beds of the liver
High pressure exit through the right atrium would take blood into pulmonary trunk to the collapsed lung (BAD IDEA)
Majority of blood goes to left atrium through the foramen ovale bypassing the developing lung

128
Q

How does the foramen ovale close at birth?

A

At birth the pressures within the two atria are similar and therefore the septum primum and septum secundum are pushed together to seal the hole

129
Q

Define Epimorphic Regeneration

A

The ability to completely replace parts of the body which have been lost with an equivalent structure

130
Q

Name 3 examples of organisms that are capable of regeneration

A 
Flatworms e.g. planaria
Hydra
Insects e.g. cockroaches
Crustaceans e.g. crabs
Teleosts (bony fish)
Anuran amphibians e.g. frog
Urodele amphibians e.g. axolotl and newt
Mammals e.g. deer and mouse
131
Q

What is a blastema?

A

A blastema is a mass of undifferentiated cells that accumulates at the site of amputation

132
Q

What is the role of undifferentiated blastemal cells?

A

Blastemal cells are undifferentiated and therefore are capable of dividing, these cells can therefore multiply to increase the pool of cells available for forming new tissue

133
Q

What is one of the two possible origins for blastemal cells?

A

1) Differentiated cells adjacent to the site of amputation can de-differentiate and re-enter the cell cycle - TRUE EPIMORPHIC REGENERATION
2) Undifferentiated “stem” cells resident in or adjacent to the tissue can be activated and enter the cell cycle - STEM CELL BASED REGENERATION

134
Q

What organisms are capable of true epimorphic regeneration?

A

Urodele amphibians e.g. axolotls, newts, salamanders

135
Q

How do we know that urodeles are capable of de-differentiation?

A

Histological evidence suggests de-differentiation of tissues

136
Q

What protein is required for the de-differentiation of muscle fibres?

A

Msx1

Inhibition of Msx1 (using morpholinos) blocks the de-differentiation of muscle fibres

137
Q

How do retinoic acids work?

A

RAs bind to receptors in the cell that can translocate to the nucleus where they act as transcription factors and turn on expression of target genes

138
Q

There are two families of retinoic acid receptors, what are they and what are the subsequent members of each family?

A

The retionoic acid receptor (RAR) family - RARalpha, RARbeta, RARgamma
The retinoid X receptor (RXR) family - RXRalpha, RXRbeta, RXRgamma

139
Q

Inhibition of signalling through which RAR blocks regeneration?

A

RARbeta

140
Q

what evidence is there to support retinoic acid being the defining factor for the fate of the blastema?

A

Increases in RA change the positional identity of the cells in the blastema to more proximal identities
Experiments adding chimaeric RARs (where the ligand binding domain has been replaced with that from another receptor) into blastema cells show this to occur

141
Q

How does a cell know it is proximal?

A

some molecules are expressed in a gradient along the proximal/distal axis in the adult limb

142
Q

Name one protein whose level vary depending on position along the PD axis?

A

Prod1 - low levels in distal blastema

Distal blastema treated with RA express high levels of Prod1

143
Q

How does Meis expression differ between adult limb and blastema?

A

In adult - distal expression greater than proximal

In blastema - proximal expression greater than distal

144
Q

What regulates expression of Meis gene?

A

Retinoic acid

145
Q

How does retinoic acid ensure regeneration of only those regions lost?

A

RA signalling in the regenerating limb is able to convey positional information, via regulation of Prod1 and Meis expression, therefore allowing the replacement of only those parts that were lost

146
Q

Give an example of regeneration in mammals

A

DEER - show annual regeneration of antlers, but can not regenerate other parts of the body
MICE - late embryonic and early postnatal mice are capable of regenerating digit tips
MICE - MRL mouse is capable of regeneration of some organs

147
Q

How does digit regeneration in mice work?

A

Msx1 is expressed in the tips of the embryonic postnatal digits and mice will regenerate digits if amputated within the Msx1 expressing region
In Msx1 knockout mice, there is no regeneration following amputation

148
Q

What are the three characteristics of cancer stem cells?

A

Self-renewal, extensive proliferation and ability to differentiate into multiple cell types

149
Q

What protects the embryo?

A

Membranes - physical protection
Fluid - physical protection - shock absorbing
Immune system - typically later in development - biological protection

150
Q

What are the membranes and fluid in anamniote (fish and amphibian) embryos and what is the effectiveness of them as protection?

A

Chorion membrane and chorionic fluid - basic physical protection
Unlikely to protect against gaseous or soluble contaminants
These embryos are very vulnerable

151
Q

What are the membranes and fluid in amniote (reptiles and mammals) embryos and what is the effectiveness of them as protection?

A

Chorion, amnion, allantois and yolk sac - 4 physical barriers
Amniotic fluid - more protective against physical and chemical/gaseous insult
These embryos are still vulnerable but less so than fish and amphibian embryos (anamniotes)

152
Q

What types of environmental insults can harm the embryo?

A 
Chemicals - contaminants, solvents
Infectious agents - bacteria, virus
Pharmaceuticals
Recreational drugs
Nutrition/plants
153
Q

Define Teratogens

A

Environmental agents that can harm the developing embryo
Teratos - monster
Logos - study

154
Q

What can be the result of adverse environmental impacts on the embryo?

A

Birth defects

Anamniotes are particularly vulnerable

155
Q

What defects can the Rubella virus cause and when are the windows for infection to cause said defects?

A

Ear defects - 7-12 weeks gestation
Lense defects - 5-8 weeks gestation
Heart defects - 4-9 weeks gestation

156
Q

What is thalidomide and what are the birth defects associated with it?

A

It is a sedative drug used for morning sickness

Causes limb defects in most cases with the threshold dose in man being incredibly low compared to most lad animals

157
Q

What is the active compound of vitamin A?

A

Retinoic acid

158
Q

What congenital defects are caused by too little retinoic acid?

A

Increased miscarriage in all mammals
Lack of eye development (pigs)
Spina bifida
Loss of neurons in CNS and peripheral NS

These suggest a role in early development/implantation, and neural development

159
Q

What congenital defects are caused by too much retinoic acid?

A 
Hydrocephaly and microcephaly
Mental retardation and behavioural problems
Heart defects
Eye and ear defects
Cleft lip and palate

These suggest a role in cranial, neural and heart development

160
Q

What congenital defect is caused by maternal consumption of veratrum californicum?

A

Causes cyclopia in foetus

The active chemical inhibits Sonic Hedgehog gene function

161
Q

What are the effects of the herbicide on anamniotes?

A

atrazine is an endocrine disruptor and causes feminisation of frogs and similar results in zebrafish

ARD Year 1 (2 decks)

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