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Skeletal Development Hankin Block II Unit I


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What sort of ossification forms the clavicle?
What does the paraxial mesoderm form?
Future somites.
What are the two layers of lateral plate mesoderm?
Parietal and visceral layers.
When does skeletal development begin in the embryonic period?
Week 4.
What are cartilage and bone of the body derived from?
What does the sclerotome form?
Axial skeleton in body and some in head.
What does lateral plate mesoderm form?
Appendicular skeleton and body wall (soma)
What forms the vertebral column?
Sclerotome (mesenchyme)
What induces sclerotome formation? What secretes these proteins?
Noggin and Sonic hedgehog induce sclerotome formation and are secreted by the notochord and neural tube floor plate.
What does PAX 1 do? What expresses it?
PAX1 initiates a cascatde of cartilage and bone forming genes for vertebral column development. It is expressed by Scleretome cells.
How are the vertebrae formed?
Endochondral ossification of sclerotome regions.
How do the ribs develop?
As outgrowths of lateral processes of thoracic vertebrae.
How is the sternum formed?
First seven ribs unite ventrally to form sternum.
How many somite pairs are there? Occipital, Cervical, Thoracic, Lumbar, Sacral, coccygeal?
Occipital 4
Cervical 8
Thoracic 12
Lumbar 5
Sacral 5
Coccygeal 8-10
What forms the base of the skull?
The first cervical and occiptal somites.
How are vertebrae formed?
By fusion of sclerotome cells from two somite levels.
When do sclerotome cells surround the developing neural tube and notochord?
During week 4.
What part of each vertebrae forms a centrum (future body) around the notochord?
The ventral part.
What does the dorsal part of each vertebrae form?
Costal prcesses (transverse), vertebral arch.
WHat forms the nucleus pulposis?
What do spinal nerves pass through?
Intervertebral foramen.
What do cells from the proatlas contribute to?
Formation of basiocciptal bone and dens.
What does the normal atlas form?
The anterior arch instead of body.
What stimulates cells to express PAX1?
SHH (sonic hedgehog)
What guides ventromedial sclerotome cells to form centrum?
What does induction of the roof plate of neural tube result in?
PAX9, MSX1, and MSX2 expression.
What do PAX9, MSX1, and MSX2 do?
Guide lateral sclerotome to form dorsal vertebral arch.
How are individual vertebrae specified?
Specific combinations of Hox genes.
What is Klippel Feil syndrome?
Short neck/decreased cerical motion, multiple fused cervical somites.
What causes Hox gene misexpression?
Retinoic acid.
What activates cranial caudal gradient of hox genes?
Retinoic acid.
What causes spinal bifida (2)?
1) Failure of normal vertebral induction.
2) Failure of the neural tube to close dorsally.
What do ribs develop from? How?
Costal processes of thoracic vertebrae. Sclerotome cells migrate within somatic lateral plate mesoderm around the body curvature toward the ventral surface.
Which ribs form the sterum?
First 7
What does the sternum arise from?
A pair of cartilagenous bands around the ventral midline.
What is cleidocranial dysplasia?
Abnormal development of head. Flat wide nose, no bridge, supernumerary and unerupted teeth, aplasia of clavicles.
What is included in the appendicular skeleton?
Appendicular girdles, intrinsic limbbones.
What type of ossification forms the appendicular skeleton?
Endochondral ossification.
What does somatic lateral plate mesoderm form?
All cartilages and bones of appendicular skeleton, and the body wall.
What does the somitic sclerotome form?
All cartilages and bones of axial skeleton in the body (some in head).
When are limb buds visible?
End of week 4.
What is the mesenchyme core of limbs formed by?
Derivied from somatic layer of lateral plate mesoderm.
What surrounds the mesenchyme core of the limbs?
What are the 3 things found initially in the limb bud? What do each of them form?
Mesenchyme from lateral plate mesoderm (forms skeleton, CT, and some blood vessels)
Mesenchymal from somites (forms muscle)
Neural crest cells (forms schwann cells and melanocytes)
What is the apical ectodermal ridge? What does it do?
A thickend distal border of the limb bud that exerts an inductive influence on the underlying mesenchyme. IT prevents its differnetiation and causes it to proliferate rapidly.
What does the dorsal ectoderm of the limb bud do?
Expreses radical fringe (signalling molecule)
What does the ventral ectoderm do?
Expresse engrailed (transcription factor)
WHat is limb outgrowth initiated by?
Factors secreted by lateral plate mesoderm.
Upper limb
Lower limb
WHat induces apical ectodermal ridge formation?
Bone modeling proteins (homeobox gene MSX2)
What restricts the apical ectodermal ridge to the distal tip of thel imb?
The radical fringe (dorsal ectoderm)
What does the radical fringe induce?
What produces engrailed? What does it do?
Ventral ectoderm represses expression of the radical fringe to maintain the border.
What do FGF4 and FGF8 do?
Maintain a progress zone in the developming limp of rapidly proliferating mesenchymal cells adjacent to apical ectodermal ridge.
What happens to proximal mesenchymal cells as they move further from the AER?
Decrease rate of division and begin differentiation.
What is the zone of polarizing activity?
A cluster of cells at the posterior border of the limb (near flank)
What determines the location of the zone of polarizing activity?
Transcription factors.
What do zone of polarizing cells produce?
Retinoic acid which initiates expression of sonic hedgehog.
What happens in the absence of sonic hedgehog?
Regression of Apical ectodermal ridge.
What determines proper location of the digits?
Zone of polarizing activity.
What is the patterning along the dorsoventral axis regulated by?
Bone modeling proteins in ventral ectoderm.
What does EN1 do?
represses WNT7a expression and restricting it to dorsal ectoderm.
What does WNT7a do?
it induces LMX1 in dorsal mesenchyme and maintains sonic hedgehog expression in the zone of polarizing activity (indirectly affects anterior/posterior patterning)
What does LMX1 do?
Specifies cells to be dorsal.
What patterns limbs along the proximodistal limb?
Hoxd genes.
What do mutations in Hoxd-13 cause?
Reduction defects of digits.
What does apoptosis play a role in?
Formation of axillary region, radius/ulna, tibia/fibula.
What do specific HOX expression results from?
Combinatorial expression of SHH, FGFs and WNT7a.
What determines digit identity?
BMP concentration.
What digit has the highest/lowest BMP concentration?
Thumb = lowest
Pinky = highest
Which direction do the legs rotate? The arms?
Upper limbs rotate laterally. Lower limb rotates medially.
What arrests limb divelopment?
Removal of apical ectodermal ridge.
What is amelia?
Complete absence of limbs.
What is phocomelia?
Proximal structures absent, hands or feet attached to trunk by irregularly shaped bones.
WHen does endochondral ossifaction begin?
End of embryonic period (week 12)
What forms the joint cavity?
Surrounding cells, cartilagenous condensations, and cell death. (WNT14 appears to be the inductive signal)

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