Lecture 14: Musculoskeletal Development I Flashcards
Describe the mesenchymal origin of each major part of the skeleton
Mesodermal sclerotomes: Vertebral column, Ribs, Sternum
Lateral plate mesoderm: Limb bones, Girdles
Head mesoderm: Calvaria and base of skull
Neural crest: Facial bones
Common differentiation pathway
- Mesenchyme is induced to enter the common pathway
- Production of N-cadherins which promote mesenchymal cell condensation
- TGF-b stimulates synthesis of fibronectin and N-CAM
- Aggregated state of mesenchymal cells is stabilized
Membranous Bone Differentiation Pathway
- Requires transcription factors Runx-2 and Osx
- Mesenchymal cells differentiate into osteoblasts
Permanent Cartilage Differentiation Pathway
- Mesenchymal condensation forms chondroblasts
- Sox-9 causes chondroblasts to secrete collagen II and cartilage matrix
- Sox-9 is continually expressed in permanent cartilage
Endochondral Bone Differential Pathway
- Runx-2, ihh, and BMP-6 induce this cartilage to undergo hypertrophy
- Hypertrophic cartilage cells secrete bone proteins and vascular endothelial growth factor
- Invading blood vessels erode the hypertrophic cartilage and bring in osteoblasts to replace cartilage with bone
Describe the origin of each part of the vertebra… centrum, neural arches, and costal processes and ribs
Centrum: derived from ventral and medial parts of paired sclerotomes
Neural arches: arise from dorsal regions of sclerotomes
Costal processes/ribs:
- Proximal development depends on expression of myotomic myogenic factors Myf-5 and Myf-6
- Distal development depends on BMP signals from somatopleural mesoderm
Differentiate Hox gene boundaries for the different regions of the vertebral column
Hox 3: occipital-cervical boundary
Hox 6: cervial-thoracic boundary
Hox 9: attached-floating ribs boundary
Describe results of experiments involving Hox gene knockouts
Single Hox gene knockouts: only minor morphological effects occur
Knockout of all Hox 10 paralogues: ribs form on all the lumbar and sacral vertebrae, Hox10 represses the influence of the anterior Hox genes
Knockout of all Hox 11 paralogues: sacrum will not form, Hox11 supresses the influence of Hox10
Mutation of a single Hox gene: only produces a minor anatomical defect, where the nonfunction of an entire group produces major effects
Describe the development of the axis/atlas complex and identify the primordia
In normal development, cells from a proatlas anlage contribute to the formation of the basioccipital bone and the dens of the axis. The normal atlas forms from an anterior arch instead of the centrum. The cells that would normally form the centrum at the level of the atlas instead fuse with the axis to form the dens of the axis
What is the relationship of Hox gene expression and the development of the vertebral column?
Expression of the Hox genes begins with the first appearance of the presomitic meso- derm and for most genes persists until chondrification begins in the primordia of the vertebrae. Formation of the normal segmental pattern along the craniocaudal axis of the vertebral column is ensured by the fact that most vertebrae are specified by a unique combination of Hox genes.
How does retinoic acid affect the expression of the Hox genes and the development of the vertebral column?
Causes shifts in cranial or caudal levels in the overall segmental organization of the vertebrae if applied at specific developmental periods. Also known as Vitamin A
What are homeotic transformations?
They represent a large shift in homeotic mutants
For example…
If RA is administered early, it results in a cranial shift (the last cervical vertebra is transformed into the first thoracic vertebra)
If RA is administered late, it causes a caudal shift (thoracic vertebrae extend into the levels of the first two lumbar vertebrae)
Describe the origin of the sternum
- From lateral plate mesoderm
- Arises as a pair of cartilaginous bands
- Fused cartilaginous bands secondarily subdivide into craniocaudal elements
Describe the origin of the clavicle
- Arises from neural crest
- Follows intramembranous pathway
- One of the first bones to become ossified
What is cleiodcranial dysplasia?
The absence of clavicles in individuals with mutants in Runx-2
(Runx-2 is required for the differentiation of osteoblasts)
Describe the subdivisions of the developing skull
Neurocranium: part of skull that surrounds the brain
Viscerocranium: surrounds oral cavity and pharynx
Occipital sclerotomes: form occipital bone
Describe the generalized neurocranium/chondrochranium
- Has a cartilaginous portion and membranous portion
- Base is formed from the chondrocranium, which contains origin of occipital, sphenoid, ethmoid, and part of temporals
- Membranous part contains origin of occipital, frontals, part of temporals
Describe the generalized viscerocranium and the bones that develop from the viscerocranium
- Cartilaginous portion forms:
- Pharyngeal arch I (Merkle’s cartilage, malleus, incus)
- Pharyngeal arch II (Reichert’s cartilage, stapes, styloid)
- Membranous portion forms:
- Part of temporal, zygomatic, maxillary, nasal, lacrimal, palatine, vomer, pterygoid plates, mandible, tympanic ring
- Mostly comprised of the brachial (pharyngeal) arches
- The mesenchyme forms the viscerocranium is mostly from the neural crest
What are the 4 components of a pharyngeal arch?
skeletal element, muscles, branch of a cranial nerve, artery
Describe the origin of the various endochondral skull bones
Chondrocranium: occipital, sphenoid, ethmoid, petrous and mastoid part of temporal
Membranous Neurocranium: interparietal part of occipital, parietal, frontal, squamous part of temporal
Cartilaginous Viscerocranium: pharyngeal arches I & II
Membranous Viscerocranium: maxillary and mandible processes
Define fontanelle and describe the pathway leading to the closure of fontanelles
fontanelle = broad area of connective tissue that intersects the sutures of two or more bones
BMP stimulates widespread bone formation, but the BMP antagonist, noggin, is expressed in all embryonic sutures. Under the influence of FGF-2, noggin is downregulated in the sutures that fuse, allowing BMP-mediated bone formation to cement the two adjacent skull bones.
Conversely, the absence of local FGF-2 allows noggin to repress BMP in the sutures that are destined not to fuse.
