24 - Development of Skeletal Tissue, Spine, Ribs, and Sternum

Question 1

What are the two forms of skeletal tissue?

Answer 1

Bone and cartilage

Question 2

What is the mesenchyme of the trunk and head derived from?

Answer 2

Trunk: paraxial mesoderm and somatic mesoderm.

Head: neural crest ectomesenchyme and head mesoderm.

Question 3

What are the master genes for bone and cartilage formation?

Answer 3

Bone: RunX2 [CBFA1) osteoblast specific transcription factor

Cartilage: Sox9 is a chondroblast-specific transcription factor

These activate the expression of other genes that are activated in only bone or cartilage forming cells. These are not involved in patterning of skeletal elements.

Question 4

What occurs if an ambryo is homozygous for runX2/CBFA?

Answer 4

Null mutant with no bones.

Skull is fibrous CT.

Skeleton is calcified cartilagenous skeletol with short limbs.

Fatal.

Question 5

What is the initial step of developing supporting tissue? What else is involved in this process?

Answer 5

Initial step: condensation of preskeletal mesenchyme.

Epithelial mesenchyme interactions are involved:

• AER/mesenchyme forms the limb
• Neural tube/mesenchyme formsthe skull/vertebrae
• Notochord/mesenchyme forms the skull vertebrae

Question 6

What occurs when the skeletal tissue forming mesenchyme preskeletal condenstation expresses sox9?

Answer 6

It becomes cartilage

Question 7

How does skeletal tissue forming mesenchyme preskeletal condenstation become tissue that performs endochondrial ossification?

Answer 7

The preskeletal condensation expresses Sox9 and becomes cartilage model of bone.

That expresses to Ihh and VegF, which causes bone to replace the cartilage.

That expresses RunX2 causing endochondrial ossification.

Question 8

How does skeletal tissue forming mesenchyme preskeletal condenstation become tissue that performs intramembranous ossification?

Answer 8

Mesenchyme cells express RunX2 and begin to form bone.

This type of ossification is seen in the flat bones of the skull and face.

Question 9

What happens in your body when you have low serum Ca2+?

Answer 9

Calcium sensing receptors cause the parathyroid to release PTH.

PTH causes the kidney to make 1,25 (OH)2 D3 causing an increase in intestinal Ca absorption, and increased Ca2+ resorption in the kidneys, and increased bone Ca2+ mobilization.

Question 11

What are ossification centers?

Answer 11

Areas in the sksletal primordium where ossification begins.

Can be used as a measures of skeletal maturation and development.

Question 12

Where are the primary and secondary ossification centers? When do they occur during development?

Answer 12

Primary: initiatial center to appear; located at the shaft of long bone or center of flat bone. Appear around 7 weeks.

Secondary: Appear in perinatal, postnatal, or postpubertal period; ends of long bonds (epiphysis), heads of ribs. Close in 20-30s. Hormonal control of maturation (estrogenand thyroid hormone).

Question 13

What is bone age?

Answer 13

The amount of epiphyseal cartilage retained - comparison of bone and chronological age is a measure of skeletal growth and maturation.

Question 14

What are chracteristics of generalized skeletal tissue displasias?

Answer 14

• May affect all or part of skeleton
• Often affect growth andmay result in short or tall stature
• Often a component of the ECM is defeftive
• Often recognized genetic component

Question 15

What is mucopolysaccharidoses?

Answer 15

Defect in synthesis, storage, or transport of a particular lysosomal enzyme; results in accumulation of substrate.

Question 16

What is marfans syndrome?

Answer 16

Alteration of fibrillin production

Question 17

How can increased or decreased growth hormone impact skeletal growth?

Answer 17

Increased: gigantism

Decreased: pituitary infantilism (type of dwarfism).

Question 18

What can increased thyroid hormone lead to?

Answer 18

Cretinism (type of dwarfism).

Question 19

What condition is associated with a mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3)?

Answer 19

Achondroplasia: failure of endochondral ossification

Question 20

In the trunk, what do the paraxial and somatic mesoderm form?

Answer 20

Paraxial mesoderm: vertebral colum and ribs

Somatic mesoderm: sternum and limb skeleton

Question 21

What are vertebrae derived from?

Answer 21

Scleratome cells

Question 22

How do scleratomes form vertebrae?

Answer 22

1. They organize into cranial and caudal subdividions with loose and dense areas of sclerotome divided by non-ebner’s fissures.
2. Re-segmentation occurs so loose area of one sclerotome unites with a dense area of another to form vertebral precursor.
3. Muscles attach to multiple tissues so the muscle can act on adjacent vertebra

Question 23

How is scleratome tissue arranged?

Answer 23

It has specific regions (central, ventral, dorsal, lateral, etc) that will become particular locations on the vertebrae.

Question 24

What do the cells of the cranial (anterior) half of the scleratome contribute to?

Answer 24

Vertebral body, small parts of the neural arch and distal rib (in thoracic region).

Question 25

What do the cells of the caudal (posterior) half of the scleratome contribute to?

Answer 25

Vertebral body, transverse processes, most of the neural arch and proximal part and main part of distal rib (in thoracic region).

Question 26

Describe the patterning of forming vertabrae?

Answer 26

**Axial patterning (cranial-caudal axis) influences the type of vertebrae that are formed.** This is thought to be controlled by the hox genes and retinoic acid expressed in this axis. * ie the pattern of signals you get determines what type of vertebrae is formed

Question 27

How do forming vertebrae ossify?

Answer 27

There are 3-4 primary centers (by week 8): 2 at the centrum and one at each arach. Closure of the neurocentral junction is at 3-6 years. Secondary centers for at puberty.

Question 28

What are two problems of abnormal regionalization that can occur in the development of the vertebral column?

Answer 28

**Abnormal regionalization due to fusion**: Klippel-Fiel sequence **Abnormal regionalization due to change in numbe**r: Lumbarization (loss of sacral vertebrae-more severe) or sacralizaton (fusion of vertebrae)

Question 29

What is dysraphism? What two diseases can be seen?

Answer 29

**Open vertebral column** due to failure of fusion of the spinous process. _Rachischisis:_ spine division - extensive opening with CNS involvement _Spinfa bifida:_ variation in length of opening

Question 30

What role does folic acid play in development?

Answer 30

Folate functons as a coenzyme that helps with the closure of the neural tube. **Taking folate prevents neural tube defects.** Without folate: anenecphalopathy (portiong of skull absent) and spina bifida may occur

Question 31

What are the two types of abnormal vertebrae formations? What is the worest case scenario when someone has scoliosis?

Answer 31

Hemi-vertebrae and block vertebrae (fused) Worse case: hemivertabrea on one side and a fusion on the contralateral side. Very unstable.

Question 32

What are two congenital defects that result in vertebral asymmatry?

Answer 32

Congenital kyphosis and congenital lordosis.

Question 33

Describe the formation of the ribs?

Answer 33

Lateral extension of costal process in the thoracic region.

Question 34

How does the sternum form?

Answer 34

Sternal bands fuse to become cartilage sternum, which ossifies to become an ossified sternum.

Question 35

What are two things that can occur with abnormal development of the ribs?

Answer 35

**Presence of an accessory rib**, which may interfere with the brachial plexus. **Abnormal rib**: ie fused or forked

Question 36

What are two potential developmental defects of the sternum?

Answer 36

Pectus excavatum (hollow) Pectum carinatum (keep-shaped)

Question 37

The vertebrae and ribs form from ______ \_\_\_\_\_\_, and the sternum forms from _______ \_\_\_\_\_\_.

Answer 37

Vertebrae and ribs: paraxial mesoderm Sternum: somatic mesoderm

Question 38

Primary ossification centers form in the vertebrae, ribs, and sternum during \_\_\_\_\_\_\_\_, while secondary centers form in the vertebrae during \_\_\_\_\_\_.

Answer 38

Primary: fetal life Secondary: puberty