L13 - Chondrogenesis Flashcards
(102 cards)
1
Q
What is the cranioacial skeleton derived from
A
Cranial neural creast cells
2
Q
What skeleton is derived from the somites
A
Axial skelton
3
Q
What is the limb skeeleton derved from
A
Lateral mesoderm
4
Q
What is the axial skeleton derived from
A
Somites
5
Q
What are components of the axial skeletons
A
Vertebral coliumns
Ribs
6
Q
What is the axial skeleton formed from
A
Paraxial mesoderm - from the somites
7
Q
What genes control segement idnetiy
A
Hox
8
Q
what gene gives the boundary between the cervical and liumbar vertebrae
A
Hox C5 and Hox C6
9
Q
As well as segement identity what else do the Hox genes control
A
Cell proliferation
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
11
Q
Where is the sclerotome induced
A
The ventral domain of the somite
12
Q
What does the dorsal domain of the somite form
A
Responsible for the formation of muscle
13
Q
Ossification of the axial skelteton is known as
A
Ossification
14
Q
What is the order of cells that are involved in chondrogenesis
A
Stem cells Sclerotomal cells Chondroblasts Chondrocytes Hypertophic chondrocytes
15
Q
Describe specification in chondrogenesis
A
Stem cells to sclerotomal cells
16
Q
Describe determination in chondrogenesis
A
Sclerotomal cells to chondroblasts
17
Q
Describe differentiation in chondrogenesis
A
Sclerotomal cells to chondrocytes
18
Q
Describe maturation in chondrogenesis
A
Chondrocytes to hypertrophic chondrocytes
19
Q
Pax stands for
A
Paired box genes
20
Q
What pax genes involved in myogensis
A
Pax 3/7
21
Q
What Pax genes involved in chondrogenesis
A
Pax 1/9
22
Q
What is the difference between Pax 1/9 and Pax 3/7
A
Pax 1/9 has the single DNA binding domain
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
24
Q
Where are Pax 1/9 expredded
A
In the ventral somite as it undergoes and epithelial to mesenchymal trnasition
25
Describe the expression of Pax1
More strongly expressed in the medial domain
26
Describe the expression of Pax9
More storngly expressed in the lateral domain
27
Describe the phenotype of a Pax1 KO mouse
Mice viable
| Abnormalities seen in vertebral column, sternum and scap
28
What skeleton is affected in a PAX 1 Knockout
Axial skeleton
29
What is the phenotypic effect of a Pax9 KO
Mice die shortly after birth
| Skeletal abnormalities
30
What skeletons are affect in a Pax9 KO
Craniofacial, visceral and limb skeletons
31
What is the pheenotype of a double Pax 1/9 KO
Mice completly lack derivatives from the medial sclerotome
32
What structures are mssing in the Pax 1 and 9 double KO
Vertebral bodies, intervertebral discs and proximal ribs
33
What are Pax 1/9 required form
Development of the medial sclerotome
34
What strucutures remain as normal in the Pax 1 9 knockout
Neural arches
35
Neural arches derived from the
Dorsal slcerotome
36
Ventral bodies derived from
Medial sclerotome
37
Proximal rib deriived from the
Lateral sclerotome
38
Distal vertebral ribe derived from the
Medial dermomyotome
39
Sternal rib derived from the
Lateral dermomyotome
40
What two signals are reuqired for the formation of the scleretome
Shh
| BMP4
41
What is the function of Shh in sclerotome formation
diffuses into the ventral part of the somite inducing expression of Pax 1 and 9
42
An Shh mutant phenotype is similar to what other KO - why?
Similar to Pax1/9 KO
Since Shh is required to induce the expression of Pax1/9 there is no induction `
43
BMP4 from the ....
What is its role
Lateral plate
Restricts the diffusion of Pax1
44
Pax1 is found in the _______
this is due to the action of
Medial domain
BMP4 from the lateral plate mesoderm
45
Somites generate the
Axial skeleton
46
Pax1/9 are essential for the
Formation of the axial keleton
47
Shh and BMP4 are involved in the
Induction and patterning of Pax1/9 expression
48
What 3 key events happen in the sclerotomal cells
Migration of the cells around the notochord
Downregulation of Pax1/9
Condensation of cells (expression of ECM proteins)
49
What 3 key events happen in the chondroblasts
Proliferation induced by BMP2/4/5
Production of the cartilage matrix
This requires Sox9
50
Proliferaition of the chondroblasts requires
BMP2/4/5
51
Production of the cartilage matrix requires
Sox9
52
What is sox9
A HMG box transcription factor
53
To form the vertebrae _________ cells ______ around the _______-
Sclerotomal cells
Condensate
Neural tube
54
How many methods of ossificiation
2
55
Name the two methods of ossification
Intramembranous
| Endochondral
56
What is intramembranous ossification
Where no cartilage is formed - direct to bone
57
What is the steps in intramembranous ossification
Mesenchymal --> nodules --> Osteoblasts --> Osteocytes --> Bone
58
Where is intramembranous ossification used most commonly
Ossification of the bones of the skull
59
What is the 2nd method of ossification
Endochrondral method
60
Where is endochondral ossification most commonly seen
Most bones - e.g. the limbs
61
What is they key point RE endochondral ossiication
Bone develops through the replacement of cartilage
62
Process of endochondral ossification
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
Whilst endochondral ossification is occuring what can be said of the extremities
Left untouched
64
One region remains untouched - what is this
Growth plate
65
What does the growth plate have a role in
Post natal growth of bones
66
What is the significance of the condrocytes undergoing apoptosis
Allows the invasion of blood vessels and osteoblasts
| Formation of the bone marrow
67
What is CD
Campomelic dysplasia
68
CD caused by a mutation in
Sox9
69
What is the phenotype shown by Cd
Dominant
70
Describe what would be seen by a person (-/-) for Sox9 --> has CD
Babies die during perinatal due to skeltal abnormalities CARTILAGE DEFECTS
71
What skeltal abnormalities
Airway cartilage is deffective, ribcage small, vertebrae are abnormal
72
Mice heterguos for Sox9 exhibit
Most of the abnormalities seen in CD patients
73
What is the molecular mechanism involving Sox9 which gives rise to CD
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
CCD
Cleoidocranial dysplasia
75
CCD caused by mutations in
Runx2
76
Inheritance pattern of CCD
Dominant
77
CCD characterised by defects in
Endochondral and intermemranous ossification
78
Runx2 is a
Critical regulator of bone formation
| Crtical TF for toblast and chondrocyte MATURATION
79
What does Runx2 interact with
Osterix
80
What is osterix
A ZF TF exp in the osteoblasts
81
What is seen in Osx deficient mice
Complete absence of oseotblast differentiation but no abnormaliity in chondrocytes dif and mat
82
What is the action of Sox9 on mesenchymal cells
Condensation
83
What is required for mesenchymal condensations to form chondrocytes
Sox9, Sox5, Sox6
84
What is required for the maturation of chondrocytes to hypertrophic chondrocytes
Runx2
85
What can inhibit the maturation of chondrocytes
Sox9
86
What is required for mesenchymal condensations to form osteoblasts
Runx2 Osterix
87
What is required for osetoblasts to form osteocytes
Runx 2 and osterix
88
The action of Sox9/5/6 on mesenchymal condensations has what effect
Formation of chondrocytes
89
Effect of RunX2 on chondrocytes
Inhibits maturation
90
Effect of Runx2 and osterix on mesenchymal condensation
Formation of osteoblasts
91
Effect of RunX2 and osterix on osteoblasts
Formation of osteocytes
92
Growth of long bones depends on the
Growth plate
93
What is contained within the growth plate
All of the progenitors required
94
What is the signalling pathway involved at the growth plate
FGFR3 -/ Ihh --> PTHrP
95
PTHrP
Parathyroid hormone related protein
96
Signalling in the growth plate is an example of
Negative feedback
97
Describe the effect ON THE SIGNALLING PATHWAY of a gain of function mutation in FGFR3
Constant inhibition of Ihh so no PTHrP
98
What is the phenotypic effect of a gain of function mutation in FGFR3
Consitiuite activation leads to dwarfism since there is promotion of chondroblasts but these fail to form bones
99
Mutations in PTHrP cause ...
Why?
Dwarfism
Fail to control the maturation of chondroblasts into chondrocytes
100
Ihh is important for the
Production and secretion of PTHrP
101
What is the mechanism for maintainining a continuous pool of progenitors in the growth plate
Prehypertrophic chocndrocytes secrete Ihh
Acts of the perichondrium
Release of PTHrP
PTHrP prevents progression of chondroblasts
Maintains a pool
102
What may also be present to aid the post natal grwoth of the muscle
Stem Cells
