Mesoderm Development Flashcards

(86 cards)

1
Q

How does the Primitive groove from

A

posterior to anterior, starting at the node (organiser)

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2
Q

How does Mesoderm move / form in gastrulation

A

Epiboly of Epiblast into primitive groove pushes Mesoderm into the centre of the embryo

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3
Q

what are the 4 types of mesoderm and what do they give rise to

A

Axial - Notochord
Paraxial - Somites
Intermediate - Kidneys
Lateral - Limbs

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4
Q

How were cell fate maps created for mesoderm tissues

A

Dye injections for lineage tracing

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5
Q

Structure of Somites

A

Highly organised
Separated structures
Repeated

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6
Q

What does the No. of Somites dictate

A

The no. of vertebrae, which is fixed for each species

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7
Q

Do somites start appearing anteriorly of posteriorly

A

Anteriorly

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8
Q

When does somitogenesis occur

A

At the same time paraxial mesoderm is forming

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9
Q

How is the timing of Somite formation conserved between species

A

Each species have a fixed time for somite formation

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10
Q

How long does somite formation take in Mice, Chicks and zebrafish

A

MIce- 120min
Chick- 90min
Zebrafish- 45min

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11
Q

Generally how do somites form

A

By budding off of pre-somatic mesoderm

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12
Q

What must cells in the pre-somatic mesoderm respond to, to create somites

A

Positional info
Mechanism that coordinates paired formation
Mechanism that generates anterior boundary
Mechanism that generates posterior boundary
Formation of cleft

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13
Q

What model explains somite formation

A

Clock wavefront model - A clock ticks in posterior pre-somatic mesoderm that drives a molecular occilator that dictates periodicity of somites.
Where cells hit the travelling wavefront, an abrupt change occurs.

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14
Q

What is the molecular occilator described in pre-somatic mesoderm

A

C-Hairy1 - chicks
(Hes - mice)
(Her - Zebrafish)

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15
Q

How are C-Hairy1 (and homologs) controlled and what do they in turn control

A

They are targets of Notch signalling
They are broken down by proteosomes
Dimerization of C-Hairy1 self represses its expression

They are bHLH protein transcriptional repressors

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16
Q

How many cycles of C-Hariy1 expression to cells undergo before forming somites

A

12

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17
Q

What major genes are involved in the clock mechanism

A

Notch-Delta
Wnts
FGFs

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18
Q

What is the determination front and how is it specified

A

It is the ‘line’ where cells stop occilating. This causes somite formation.

FGF8 from the node is present in posterior regions.
Retinoic Acid is present Anteriorly.
They are antagonistic to each other and create a hard boundary

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19
Q

What is the fgf8 - RA interaction

A

RA –|FGF8
FGF8–> Cyp28 –|RA

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20
Q

What causes the determination front to move

A

Convergent extension of the posterior region pushes the node further posteriorly, moving the determination form posteriorly at a regular rate.

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21
Q

How is the anterior of the forming somite patterned

A

Mesp2 is maintained in the anterior half of the somite due to tbx6 and notch

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22
Q

How is the posterior of the somite patterned

A

Cycle is stopped a bit later causing Notch signalling to be active.

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23
Q

How does the determination front stop the occilating cycle

A

FGF8 only present posteriorly before the DF is the driver of the occilation cycle. So once cells stop seeing fgf8 the cycle stops

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24
Q

How are boundaries between Somites formed and result in Budding off

A

Posterior region of somite experiences Notch signalling. After enough time, Ephrin builds up on posterior. Anterior region past the DF express Ephs as a result of Mesp2. Ephs and Ephrins are extremely antagonistic and cause tissue separation.

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25
What are MRFs
Myogenic Regulatory Factors
26
What is muscle important for
Motor function Metabolism Respiration
27
What is the overall flow of muscle creation
Stem cells are determined into Muscle progenitor cells (Myoblasts). These differentiate into Myotubes which mature into Myofibers
28
What is special about Myotubes
They are Syncytium
29
what is MyoD and How was it discovered
A Master regulator gene for Muscle fate. Discovered by comparing cDNA of fibroblasts with cDNA of Myoblast. It was know that fibroblasts could become Myoblasts using 5Aza
30
What does MyoD being a master regulator mean
It can induce myotube differentiation in any cell that sees it
31
What is the structure of MyoD and what is it's function
It is a bHLH protein. Family includes : MyoD, Myf5, Myogenin and MRF4 It is a transcriptional activator
32
Where do muscle progenitors originate from
From Somites
33
What is the dermomyotome and where is it
The epithelium of a somite which is distal to the notochord. It contains progenitors for skeletal muscles as well as trunk and limb cells
34
What Tf do skeletal muscle progenitors express
Pax3
35
What are the 2 types of dermomyotome and what do they give rise to
Epaxial - Deep back muscles Hypaxial - abdominal and limb muscles
36
What do Epaxial myotome cells express and for how long
Myf5 between day 8 and 12 of gestation MyoD from day 10 onwards
37
What do Hypaxial myotome cells express and for how long
Myf5 between day 9.5 and 12 MyoD from day 10 onwards
38
What MRFs are expressed in both Epaxial and Hypaxial cells
Myogenin and MRF4
39
What is myogenin required for
Muscle differentiation
40
What are Myf5 and MyoD required for
Myf5 OR MyoD are required to generate myoblasts
41
Why is myogenin expressed after Myf5 and MyoD
Differentiation occurs after determination into myoblasts
42
What signals does epaxial myotome see to induce determination
Sees Wnts from Ectoderm and Shh from notochord resulting in early expression of Myf5 MRF
43
What signals does Hypaxial myotome see to induce determination
Only sees Wnts from Ectoderm so MyoD becomes they main MRF signalling muscle determination
44
What causes migration od Hypaxial cells into the limb bud
Guidance by HGF (secreted by mesenchymal limb bud) as a result of pax3 expression of cMet receptor on Hypaxial cells
45
What happens when pax3 is lost
No muscle in limbs
46
What does BMP4 do to help hypaxial cell lineage
BMP4 induces Pax3 and repressed Myf5 + MyoD expression until cells arrive into the limb bud
47
What are Satelite cells and where do they originate
Cells that originate from somites that stick around in adults post birth. They act to maintain and grow muscles. They are found beneath basal lamina of muscle fibres
48
What happens when Satellite cells are stimulated by injury
They receive HGF signal which activates pax7 leading to Myf5+MyoD expression. This cell then undergoes asymmetric division to create one cell that expresses myogenin and another that replenishes the original Satellite cell
49
What does weak regeneration of satellite cells lead to
Muscle distrophy Sarcopenia
50
What does over active regeneration lead to
Cancer
51
What progenitors form the skull
Neural crest cells
52
What progenitors form the axial skeleton
Somites
53
What progenitors form the limb skeletons
Lateral Mesoderm
54
What tissues overall combine to form the skeleton
Paraxial (somites), Lateral mesoderm and neural crest cells
55
What is the axial skeleton
Includes the vertebrae and rib bones
56
What stains bones red in vivo
Alizarin
57
What stains cartilage blue in vivo
Alcian
58
What further patters Somites along the A-P axis
Hox genes
59
What allows hox genes to create different sized vertebras we see in Mammals
Hypothetically they control cell proliferation
60
What cells in somites does axial skeleton form from
epithelial somite cells that are proximal to the notochord. Sclerotome
61
What process causes formation of sclerotome
It undergoes an epithelial to mesenchymal transition
62
What does sclerotome express
Pax1 and 9
63
How do somite cells tell the difference from undergoing chondrogenesis due to pax1/9 instead of myogenesis due to pax3/7
Pax 1/9 have less specificity than pax3/7 so chondrosite expression is limited to areas with high pax 1/9
64
What causes differential location of pax1 and pax 9 in sclerotome
Shh from the notochord is strong in regions proximal to its origin, causing expression of pax1 instead of pax9 BMP inhibition of Shh from lateral plate causing pax9 expression in distal sclerotome
65
What structures arise from pax1 sclerotome
Vertebral columns Sternum Scapula
66
What structures arise from pax9 sclerotome
Skull Visceral skeleton Limbs
67
Can organisms survive pax1 KO
Yes
68
Can organisms survive pax9 KO
No
69
How does dermomyotome contribute to skeleton formation
Some dermomyotome migrate and differentiate to form distal and sternal ribs
70
What does medial sclerotome form
Vertebral bodies
71
What does dorsal sclerotome form
Neural arches
72
What happens after sclerotome is induced and patterned
Pax1 and 9 are downregulated Cells condense and create ECM Chondroblasts form
73
What induces proliferation of chondroblasts
BMP2/4/5
74
What causes production of the cartilage matrix
Sox9
75
What are the two types of ossification and what happens during them?
Intramembranous. Mesenchymal cells turn directly into osteoblasts and bone Endochondral. replacement of cartilage by bone
76
Where does intramembranous ossification occur?
The Skull
77
What induces intramembranous ossification
Wnt expression causes sox9 to cause expression of Runx2
78
What induces Endochondral ossification and chondrocyte formation
Sox9 continues expression normally due to no Wnt signalling
79
What causes chondrocytes to become hypertrophic
late expression of Runx2
80
What happens after chondrocytes become hypertrophic
They die by apoptosis and blood vessels enter the cartilage matrix
81
What replaces chondrocytes after they die
Osteoblasts
82
What do osteoblasts form as cartilage disappears
The primary ossification centre
83
How does the secondary ossification centre form
Blood vessels penetrate the ends of the bone
84
What happens after the secondary ossification centre is formed
The primary ossification centre becomes the growth plate
85
What happens in the growth plate
Germinal zone between primary and secondary ossification centres contains stem cells. These differentiate and follow the same fate path as Endochondral ossification. Osteoblasts form and are then invaded by capillaries
86
What molecules cause events in the growth plate
Ihh from hypertrophic zone causes expression of PTHrP in germinal zone. PTHrP in the germinal zone inhibits cells from going hypertrophic.