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BMS242 Developmental Biology > L13 - Chondrogenesis > Flashcards

L13 - Chondrogenesis Flashcards

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1
Q

What is the cranioacial skeleton derived from

A

Cranial neural creast cells

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2
Q

What skeleton is derived from the somites

A

Axial skelton

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3
Q

What is the limb skeeleton derved from

A

Lateral mesoderm

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4
Q

What is the axial skeleton derived from

A

Somites

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5
Q

What are components of the axial skeletons

A

Vertebral coliumns

Ribs

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6
Q

What is the axial skeleton formed from

A

Paraxial mesoderm - from the somites

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7
Q

What genes control segement idnetiy

A

Hox

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8
Q

what gene gives the boundary between the cervical and liumbar vertebrae

A

Hox C5 and Hox C6

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9
Q

As well as segement identity what else do the Hox genes control

A

Cell proliferation

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10
Q

What are the three main steps which lead to the formation of axial skeleton

A

Sclerotome induction
Cartilage formation
Ossification of axial skeleton

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11
Q

Where is the sclerotome induced

A

The ventral domain of the somite

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12
Q

What does the dorsal domain of the somite form

A

Responsible for the formation of muscle

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13
Q

Ossification of the axial skelteton is known as

A

Ossification

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14
Q

What is the order of cells that are involved in chondrogenesis

A 
Stem cells 
Sclerotomal cells 
Chondroblasts 
Chondrocytes 
Hypertophic chondrocytes
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15
Q

Describe specification in chondrogenesis

A

Stem cells to sclerotomal cells

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16
Q

Describe determination in chondrogenesis

A

Sclerotomal cells to chondroblasts

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17
Q

Describe differentiation in chondrogenesis

A

Sclerotomal cells to chondrocytes

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18
Q

Describe maturation in chondrogenesis

A

Chondrocytes to hypertrophic chondrocytes

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19
Q

Pax stands for

A

Paired box genes

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20
Q

What pax genes involved in myogensis

A

Pax 3/7

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21
Q

What Pax genes involved in chondrogenesis

A

Pax 1/9

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22
Q

What is the difference between Pax 1/9 and Pax 3/7

A

Pax 1/9 has the single DNA binding domain

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23
Q

What is the first question that must be adressed when llooking at whether Pax 1/9 have a role in chondrogenesis

A

Are they expressed at the right place at the right time

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24
Q

Where are Pax 1/9 expredded

A

In the ventral somite as it undergoes and epithelial to mesenchymal trnasition

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25
Q

Describe the expression of Pax1

A

More strongly expressed in the medial domain

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26
Q

Describe the expression of Pax9

A

More storngly expressed in the lateral domain

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27
Q

Describe the phenotype of a Pax1 KO mouse

A

Mice viable

Abnormalities seen in vertebral column, sternum and scap

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28
Q

What skeleton is affected in a PAX 1 Knockout

A

Axial skeleton

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29
Q

What is the phenotypic effect of a Pax9 KO

A

Mice die shortly after birth

Skeletal abnormalities

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30
Q

What skeletons are affect in a Pax9 KO

A

Craniofacial, visceral and limb skeletons

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31
Q

What is the pheenotype of a double Pax 1/9 KO

A

Mice completly lack derivatives from the medial sclerotome

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32
Q

What structures are mssing in the Pax 1 and 9 double KO

A

Vertebral bodies, intervertebral discs and proximal ribs

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33
Q

What are Pax 1/9 required form

A

Development of the medial sclerotome

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34
Q

What strucutures remain as normal in the Pax 1 9 knockout

A

Neural arches

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35
Q

Neural arches derived from the

A

Dorsal slcerotome

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36
Q

Ventral bodies derived from

A

Medial sclerotome

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37
Q

Proximal rib deriived from the

A

Lateral sclerotome

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38
Q

Distal vertebral ribe derived from the

A

Medial dermomyotome

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39
Q

Sternal rib derived from the

A

Lateral dermomyotome

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40
Q

What two signals are reuqired for the formation of the scleretome

A

Shh

BMP4

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41
Q

What is the function of Shh in sclerotome formation

A

diffuses into the ventral part of the somite inducing expression of Pax 1 and 9

42
Q

An Shh mutant phenotype is similar to what other KO - why?

A

Similar to Pax1/9 KO

Since Shh is required to induce the expression of Pax1/9 there is no induction `

43
Q

BMP4 from the ….

What is its role

A

Lateral plate

Restricts the diffusion of Pax1

44
Q

Pax1 is found in the _______

this is due to the action of

A

Medial domain

BMP4 from the lateral plate mesoderm

45
Q

Somites generate the

A

Axial skeleton

46
Q

Pax1/9 are essential for the

A

Formation of the axial keleton

47
Q

Shh and BMP4 are involved in the

A

Induction and patterning of Pax1/9 expression

48
Q

What 3 key events happen in the sclerotomal cells

A

Migration of the cells around the notochord
Downregulation of Pax1/9
Condensation of cells (expression of ECM proteins)

49
Q

What 3 key events happen in the chondroblasts

A

Proliferation induced by BMP2/4/5
Production of the cartilage matrix
This requires Sox9

50
Q

Proliferaition of the chondroblasts requires

A

BMP2/4/5

51
Q

Production of the cartilage matrix requires

A

Sox9

52
Q

What is sox9

A

A HMG box transcription factor

53
Q

To form the vertebrae _________ cells ______ around the _______-

A

Sclerotomal cells
Condensate
Neural tube

54
Q

How many methods of ossificiation

A

2

55
Q

Name the two methods of ossification

A

Intramembranous

Endochondral

56
Q

What is intramembranous ossification

A

Where no cartilage is formed - direct to bone

57
Q

What is the steps in intramembranous ossification

A

Mesenchymal –> nodules –> Osteoblasts –> Osteocytes –> Bone

58
Q

Where is intramembranous ossification used most commonly

A

Ossification of the bones of the skull

59
Q

What is the 2nd method of ossification

A

Endochrondral method

60
Q

Where is endochondral ossification most commonly seen

A

Most bones - e.g. the limbs

61
Q

What is they key point RE endochondral ossiication

A

Bone develops through the replacement of cartilage

62
Q

Process of endochondral ossification

A

Chondrogenesis formation of a cartilagenous model of the bone
Chondrocytes stop dividing and become hypertrophic
Death of chondrocytes - space invaded by BV and osteoblasts - BONE MARROW
Osteoblasts replace cartilage and form the primary ossification centre
Blood vessels enter the epiphyses
Secondary ossification centres formed in the cartilage plate between epophyssi and diaphysis

63
Q

Whilst endochondral ossification is occuring what can be said of the extremities

A

Left untouched

64
Q

One region remains untouched - what is this

A

Growth plate

65
Q

What does the growth plate have a role in

A

Post natal growth of bones

66
Q

What is the significance of the condrocytes undergoing apoptosis

A

Allows the invasion of blood vessels and osteoblasts

Formation of the bone marrow

67
Q

What is CD

A

Campomelic dysplasia

68
Q

CD caused by a mutation in

A

Sox9

69
Q

What is the phenotype shown by Cd

A

Dominant

70
Q

Describe what would be seen by a person (-/-) for Sox9 –> has CD

A

Babies die during perinatal due to skeltal abnormalities CARTILAGE DEFECTS

71
Q

What skeltal abnormalities

A

Airway cartilage is deffective, ribcage small, vertebrae are abnormal

72
Q

Mice heterguos for Sox9 exhibit

A

Most of the abnormalities seen in CD patients

73
Q

What is the molecular mechanism involving Sox9 which gives rise to CD

A

Sox9 may inhibit maturation of proliferating cells
Sox9 can bind and activate promoters of chondrocyte-specific genes - Sox9 an important regulator of differentiation and maturation of chondrocytes

74
Q

CCD

A

Cleoidocranial dysplasia

75
Q

CCD caused by mutations in

A

Runx2

76
Q

Inheritance pattern of CCD

A

Dominant

77
Q

CCD characterised by defects in

A

Endochondral and intermemranous ossification

78
Q

Runx2 is a

A

Critical regulator of bone formation

Crtical TF for toblast and chondrocyte MATURATION

79
Q

What does Runx2 interact with

A

Osterix

80
Q

What is osterix

A

A ZF TF exp in the osteoblasts

81
Q

What is seen in Osx deficient mice

A

Complete absence of oseotblast differentiation but no abnormaliity in chondrocytes dif and mat

82
Q

What is the action of Sox9 on mesenchymal cells

A

Condensation

83
Q

What is required for mesenchymal condensations to form chondrocytes

A

Sox9, Sox5, Sox6

84
Q

What is required for the maturation of chondrocytes to hypertrophic chondrocytes

A

Runx2

85
Q

What can inhibit the maturation of chondrocytes

A

Sox9

86
Q

What is required for mesenchymal condensations to form osteoblasts

A

Runx2 Osterix

87
Q

What is required for osetoblasts to form osteocytes

A

Runx 2 and osterix

88
Q

The action of Sox9/5/6 on mesenchymal condensations has what effect

A

Formation of chondrocytes

89
Q

Effect of RunX2 on chondrocytes

A

Inhibits maturation

90
Q

Effect of Runx2 and osterix on mesenchymal condensation

A

Formation of osteoblasts

91
Q

Effect of RunX2 and osterix on osteoblasts

A

Formation of osteocytes

92
Q

Growth of long bones depends on the

A

Growth plate

93
Q

What is contained within the growth plate

A

All of the progenitors required

94
Q

What is the signalling pathway involved at the growth plate

A

FGFR3 -/ Ihh –> PTHrP

95
Q

PTHrP

A

Parathyroid hormone related protein

96
Q

Signalling in the growth plate is an example of

A

Negative feedback

97
Q

Describe the effect ON THE SIGNALLING PATHWAY of a gain of function mutation in FGFR3

A

Constant inhibition of Ihh so no PTHrP

98
Q

What is the phenotypic effect of a gain of function mutation in FGFR3

A

Consitiuite activation leads to dwarfism since there is promotion of chondroblasts but these fail to form bones

99
Q

Mutations in PTHrP cause …

Why?

A

Dwarfism

Fail to control the maturation of chondroblasts into chondrocytes

100
Q

Ihh is important for the

A

Production and secretion of PTHrP

101
Q

What is the mechanism for maintainining a continuous pool of progenitors in the growth plate

A

Prehypertrophic chocndrocytes secrete Ihh
Acts of the perichondrium
Release of PTHrP
PTHrP prevents progression of chondroblasts
Maintains a pool

102
Q

What may also be present to aid the post natal grwoth of the muscle

A

Stem Cells

BMS242 Developmental Biology (17 decks)

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