Somitogenesis & musculoskeletal dev.

Question 1

What are somites?

Answer 1

building blocks that give rise to a number of organs and systems in the body, including the musculoskeletal system

Question 2

Abnormal somitogenesis can cause what?

Answer 2

skeletal abnormalities & embryonic death

Question 3

Somites are derived from which of the 3 body layers? Specifically… what structures/tissues are derived from it?

Answer 3

Paraxial mesoderm (via condensation) -> connective tissue, bone, muscle, cartilage

Question 4

Structurally, what do somites look like?

Answer 4

paired spherical structures running along either side of neural tube

Question 5

The mature somite has 4 cell types. List them & the structures they go on to form…

Answer 5

1. Sclerotome - vertebrae & rib cage
2. Myotome - musculature of back ribs & limbs
3. Dermatome - dermis of the back
4. Syndetome - tendons & blood vessels

Question 6

T or F - somites form anterior to posterior gradient

Answer 6

true

Question 7

Why is boundary formation critical for somitogenesis?

Answer 7

Cos if it’s fucked -> disrupts Notch signalling, alteration in skeletal muscle dev., failure of thoracic vertebrae to seperate, & associated structures fail to form

Question 8

Explain how somites are formed. Which factors are involved?

Answer 8

somites start as condensations of mesenchymal cells

After seperation, fibronectin & N-cadherin organises ‘inner’ mesenchymal & ‘epithelial’ components

Question 9

Myoblast precursor cells…what structures do they form?

Answer 9

Abaxial myoblasts -> body wall, limbs, tongue

Question 10

Future satellite cells arise from? Functions?

Answer 10

Arise from central myotome & function in postnatal muscle growth & repair

Question 11

What determines (globally) what muscles / skeletal components will be produced? 2 factors…

Answer 11

• Hox genes

- AP axis specification

Question 12

What determines (within the somite) what muscles / skeletal components will be produced? 2 factors…

Answer 12

• Shh

- Pax1

Question 13

List the steps in muscle tissue generation from myoblasts (A-F) some factors involved…

Answer 13

A. Myotome cells (via MyoD, Shh, Myf5) -> dividing myoblasts
B. Dividing myoblasts (via FGFs) -> cell alignment
C. Cell alignment (Cell adhesion molecules - CAM) -> initial myotube formation
D. initial myotube formation (via muscle specific proteins) -> myotube maturation
E. myotube maturation (Interleukin-4) -> (F) muscle fiber & stem cell
F. Muscle fiber & stem cell

Question 14

What are the 2 major modes of bone formation?

Answer 14

Intramembraneous ossification

Endochondral ossification

Question 15

Describe Intramembraneous ossification…

Answer 15

Mesenchymal cells condense to form osteoblasts which lay down an (osteoid) collagen proteoglycan matrix that is able to bind calcium. Osteoblasts then become embedded in the matrix and become osteocytes.
Process involves BMP’s (bone morphogenetic proteins) and a transcription factor CBFA1 (Can’t Be Faaarked 1)

Question 16

Describe Endochondral ossification…

Answer 16

Occurs primarily in the vertebral column, ribs, pelvis and limbs
Involves formation of cartilage from aggregations of mesenchymal cells, then replacement of cartilage with bone.
Has 5 phases…

Question 17

5 phases of endochondral ossification…some factors involved…

Answer 17

1. Commited cartilage - mesenchymal cells commit to becoming cartilage (Shh, Pax1)
2. Committed mesenchymal cells condense -> nodules & differentiate -> chondrocytes (BMP, Sox9)
3. Chondrocytes proliferate and create cartilage model of the bone (secretion of cartilage specific ECM)
4. Chondrocytes stop proliferating and increase their cellular volume
5. Enlarged chondrocytes alter secretion of ECM to enable calcification by calcium Phosphate
6. cells differentiate into osteoblasts. Blood vessels invading the bone bring in osteoblasts and chondroclasts which remove dead cell (chondrocyte) debris