MSK Embryology

Question 1

Define gastrulation

Answer 1

Epilast ingression through the primitive streak to form a three layered structure - trilaminar disk - ecto, meso and endoderm

Question 2

What is neurulation?

Answer 2

Ectodermal cells fold and regulated by transcription factors to form the nervous system

Question 3

What is the origin of most musculoskeletal features in the head and neck?

Answer 3

Ectomesenchyme
Originating from neural crest cells

Question 4

What is the different basic origin of the skull?

Answer 4

The frontal and temporal part of the skeleton - neural crest-derived structures (EMT is ventral and lateral)
Occipital and parietal - mesdermal tissues

Question 5

What are the two different ways bone can form in the skull?

Answer 5

Intramembranous ossification
Endochondral ossification

Question 6

What is endochondral ossification?
What parts of the skull does it form?

Answer 6

Cartilage that ossifies
Contributes to the viscerocranium and the chondrocranium.
(sphenoids, part of occipital, otic capsules and nasal capsules)
Bones of facial expression (maxilla, mandible, vomer, zygomatic)

Question 7

What are the bones of the viscerocranium?

Answer 7

Lacrimal
Nasal
Zygomatic
Ethmoid
Vomer
Inf nasal concha
Maxilla
Mandible

Question 8

What are the implications of the cranial vault forming by intramembranous ossification?

Answer 8

Limited ability to increase further in size - bones tend to reach a fixed ossification and size early in life
Reduces room for bone growth
Means the majority of growth occurs as the cranial sutures and fontanelles -> these contain mesenchymal precursors that have not yet undergone ossification.
One of the reasons for large variability in head and skull shape

Question 9

What is craniosynostosis?

Answer 9

Abnormal head shape
Due to premature fusion of head sutures.
As the brain continues to grow witll push out in other directions causing abnormal patterns of head growth in alternative suture weakness areas.

Question 10

What signalling molcule mainly regulates the formation of bone?

Answer 10

FBG 2>3>1 for bone cells
FGF signalling drives differentiation of mesenchyme into osteoblasts, high levels of functional FGF molecules and receptors are required for osteogenic differentiation.

Question 11

What mutation is considered to cause craniosynostosis?

Answer 11

Mutations in the FGF signalling molecules or receptors.

Question 12

What are some examples of craniosynostosis?

Answer 12

Scaphomegaly
Brachycephaly
Trigoncephaly
Plagocephaly

Question 13

What is scaphomegaly?

Answer 13

Premature fusion of the sagittal suture
results in forward growth of the skull

Question 14

What is brachycephaly?

Answer 14

Premature fusion of the coronal suture
Results in abnormal lateral growth of the skull
(BUtch on the sides)

Question 15

What is trigoncephaly?

Answer 15

Premature fusion of the frontal suture
Triangle shaped skull - growth out at the back of the skull (occipital area)

Question 16

What is plagocephaly?

Answer 16

Fusion of coronal suture on one side
Point - curves to opposite side at the front

Question 17

What cell populations contribute to the development of the axial MSK?

Answer 17

Paraaxial mesoderm

Question 18

What structures does the intermediate mesoderm differentiate into?

Answer 18

Kidney
Gonads

Question 19

What structures does the cordamesoderm differentiate into?

Answer 19

Notochord
Intervertebral disc

Question 20

What does the paraxial mesoderm develop into?

Answer 20

Somites (own slide)
Paraxial = head

Question 21

What are the different lineages of differentiation for somites?

Answer 21

Sclerotome
Dermomyotome

Question 22

What does the sclerotome differentiate into?

Answer 22

Vertebrae and ribs
Endotome = endothelial cells, dorsal aorta
Arthortome = vertebral joints
Syndetome = tendon

Question 23

What does the dermomyotome differentiate into?

Answer 23

Myotome = skeletal muscle
Dermatome = dermis, skeletal muscle
Mainly on the back

Question 24

What embryological structure forms the majority of the axial MSK system?

Answer 24

Somites

Question 25

Describe the basic anatomy that underpins the development of somites.

Answer 25

Embryo grows from the back = growth zone Cells in the tail bud/growth zone gastrulate - undergo EMT to migrate into the presomitic mesoderm then undergo a MET to become a somite

Question 26

What model describes the process of somitogenesis?

Answer 26

Clock and wave front signalling

Question 27

What is the wave front process of somitogenesis?

Answer 27

Influence of FGF8 and retinoic acid From the back - conc gradient of FGF8 From the front - conc gradient of retinoic acid (Raldh2) At mid point where FGF8 and Raldh2 are both low the Mesp gene is expressed This is a transcription factor that drives the mesenchymal to epithelial transition to form somites The point of gradient boundary is known as the wavefront/determination front. The wavefront moces as more somites are produced hence the location of max retinoic acid conc changes

Question 28

What is the role of Notch signalling in somitogenesis?

Answer 28

Forms the wave of the model Notch signalling oscillates -> is cell to cell signalling -> gaps in signalling correspond to gaps between somites Prevents formation of just one very long somite

Question 29

What is the role of Hox gene signalling in somitogenesis?

Answer 29

Controls the positional identity of each somite Uses a cranial caudal axis - relates to knowing a thoracic v a lumbar vertebrae.

Question 30

What is spinal dystosis?

Answer 30

A group of conditions characterised by abnormal development of bones in the spine and ribs - vertebrae are misshapen and abnormally fused - short torsa, restricted chest expansion and breathing difficulties.

Question 31

What is the embryological origin of the appendicular skeleton?

Answer 31

The lateral plate mesoderm

Question 32

What is the importance of positional identity in appendicular MSK development?

Answer 32

Regulated by hox genes - various combinations and concentrations gives identity Why we have legs on the bottom and arms on the top

Question 33

What process controls the outgrowth of limbs? (appendicular skeleton)

Answer 33

Retinoic acid and FGF signalling gradient RA proximally and FGF distally The concentration balance regulates Hox gene expressions -> gives positional identity of the stylopod, zuegopod and the autopod.

Question 34

What are the key timing of bone development in embryology?

Answer 34

Patterning established Mesenchyme -> cartilage (begins around week 6) Primary ossification centres develop grossly at week 10 until late adolescence/early adulthood Continues through secondary ossification centres into adulthood - responsible for most bone growth between birth to adulthood.

Question 35

After birth where in the bone does most growth occur?

Answer 35

The growth plate - chondrocytes proliferate and eventually ossify.

Question 36

What signalling process regulates primary/secondary ossification centres?

Answer 36

Sox9 - specifies cartilage progenitors Runx2 - drives osteogenesis Both these transcription factors are reciprocally regulated. Ihh - drives chondrocyte proliferation FGF - inhibits proliferation nad differentiation postnatally

Question 37

What is the underlying disease process of achondroplasia?

Answer 37

Long bone dwarfism Activating mutation of FGFR3 - results in increased inhibition of proliferation and differentiation in osteogenesis postnatally. This effects endochondral ossification

Question 38

What is the embryological link to osteosarcoma?

Answer 38

Affects mianly long bones Originates from mesenchymal pluripotent stem cells Early onset as these centres of ossification are most active in childhood/teenage years.