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121 Cards in this Set

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  • Back
skeletal tissue forming mesencyme
3 Precursors of the skeleton (sources of STFM):
1. Paraxial mesoderm
2. Lateral plate mesoderm
3. Ectoderm (neural crest)
What specifically does ectoderm form in the skeleton?
structures in the head
What does STFM form at the site of bone/cartilage formation?
Preskeletal condensation
3 Factors influencing STFM differentiation:
-Epithelial-mesenchymal interactions
-Specific transcription factors
-Growth factors
2 specific transcription factors influence STFM differentiation:
Sox-9 (cartilage)

Cbfa-1 (bone)
A growth factor that acts during skeletal development:
Bone morphogenetic factor (BMP)
Specific component of paraxial mesoderm that contributes to STFM:
Scleratome of somites
Specific layer of lateral plate mesoderm that contributes to STFM:
Somatic layer
2 Pathways of bone formation:
-Intramembranous ossification

-Endochondrial ossification
Each pathway starts with:
Preskeletal Mesenchyme Condensation
1st step in forming bones:
STFM cells differentiate into CHONDROBLASTS and form cartilage
Factor that directs differentiation of STFM cells forming bones:
Cbfa-1 = intramembranous oss

Sox-9 = endochondrial oss
Steps 2-4 in forming cartilage:
2. Chondroblasts -> Chondrocytes
3. Cytes secrete matrix
4. Cartilage forms; surrounding cells are Perichondrium
2 fates of cartilage:
-Remain cartilage for life

-Form bone by intramembranous or endochondrial ossification
How does Intramembranous ossification get started?
During preskeletal condensation, osteoblasts form directly by direction of cbfa-1
What are qualities of bone that forms by intramemb ossification?
Superficial, flat, and grows by adding new bone to edge.
How does Endochondrial ossification get started?
Cartilage forms first to provide a model.
Qualities of bone formed by endochondrial ossification:
-Grows in a focused direction
Ossification centers are
sites of collagen synthesis - where ossification occurs.
What info do ossification centers give?
Bone age - indicator of skeletal growth and maturation compared to actual age of patient.
What is bone age?
The amount of epiphyseal cartilage in skeleton
Bone maturation that uses ossification centers:
both - intramemb and endochond.
2 types of ossification centers:
Primary vs. Secondary
Primary ossification centers:
-When in devo?
Prenatal - located at CENTER of bones; radiates from there.
Why does the skeleton have to develop prenatally?
To support respiration
Secondary ossification centers:
-When in devo?
Pre/postnatal, postpuberal; located at ENDS of bones; growth happens from ends->in; disappear in 20's - 30's
Axial skeleton consists of:
-Vertebral column
Vertebrae derive from:
Scleratome mesenchyme - beginning at Somite 5
Somitic mesoderm is from:
Paraxial mesoderm
3 components of somites:
4 steps in forming vertebrae:
1. Lateral scleratome moves toward neural tube
2. Some scleratome moves close to notochord = perinotochordal sheath
3. Sclrtm condenses caudally; stay loose cranially
4. Perinotoch sheath arranges too but not in line with other
Loose potion of scleratome is associated with:
spinal nerve and intersegmental artery
Components of a primitive vertebrae:
-Neural arches (pair)
What grows from the neural arches?
Costal and transverse processes
What does the centrum form from?
Loose portion of perinotochordal sheath
What is needed to form a centrum?
2 adjacent somite pairs
What do the neural arches form from?
Dense portion of scleratome
What does the compact portion of perinotochordal sheath become?
Intervertebral disc
What does the notochord become?
Stays put where it is, as the Nucleus Pulposus
___ pr of somites forms neural arches + intervertebral disc.
___ pr of somites forms centrum
1 pair

2 pairs
Primitive vertebrae are formed by:
Week 5-6
Regionalization of the spine is achieved by:
differential expression of hox genes along cranial/caudal axis
What type of ossification do vertebrae undergo?
How many 1' ossification centers develop in each vertebra?
What is the neurocentric junction?
Line between centrum and neural arches; cartilage plate remains until 3-6 yrs old.
When do secondary ossification centers form on vertebrae?
Primary ossification centers:
____/centrum which ____
___/neural arch
2/centrum - usually fuse
1/neural arch
Regionalization signals:
-Hox genes
-Retinoic acid
3 abnormalities of vertebral devo related to abnormal regionalization:
1. Klippel-feil anomaly
2. Sacralization
3. Lumbarization
Klippel-feil anomaly:
-Fused cervical vertebrae
-Short neck
-Low hair line
Change in # of a TYPE but not total number of vertebrae.
Defects of Asymmetry:
-Scoliosis - lateral curvature
-Kyphosis - front curvature
-Lordosis - back
General condition caused by failure of neural arches to fuse
2 types of dysraphism:
-Rachischisis (open)

-Spina bifida
What is Rachischisis?
Condition where many vertebrae have unfused processes.
What is Spina Bifida?
Series of conditions where one or a few vertebrae have unfused processes
What is the mildest form of spina bifida?
Spina Bifida Occulta
3 Defects of Formation of vertebrae:
-Wedge-shaped Vertebrae
-Unsegmented Bars
What can cause hemivetebrae to form?
Failure of primary ossification centers to develop
How do ribs develop?
By lateral expansion of costal process in thoracic spine region
How does the sternum develop?
The ribs come together with 2 Sternal Bands and push them together to form the Sternum.
What is the most common form of accessory ribs? Who is it more common in?
Lumbar ribs - 3x more common in males.
2 divisions of the skull:
-Neurocranium (brain cavity)
-Viscerocranium (face/jaw)
Neurocranium consists of:
-Chondrocranium (floor)
-Calvaria (skull cap)
Viscerocranium consists of 4 basic types of bones:
(how do they ossify?)
-Ossicles/Styloid process via endochondral ossification

-Facial bones/Jaws via Intramembranous ossification
How many bones are in the skull?
Calvaria derives from:
Neural crest
Chondrocranium (floor) derives from:
Paraxial mesoderm
Face/jaws derive from:
How does each ossify:
Calvaria: intramembranous
Chondrochranium: endochondral
-derived from?
-How does it form?
-Mesoderm (scleratom)
-Forms by fusion of several chondrogenic centers
What allows the chondrocranium to grow longitudinally?
Spheno-ethmoidal and Spheno-occipital cartilage plates
What is the Calvaria primarily derived from?
Neural Crest Ectoderm
What are Fontanelles?
Intersections between cranial sutures that run perpendicular
What are the 4 fontanelles, and what is each one's reference pt?
Anterior - Bregma
Posterior - Lambda
2 Anterolateral - Pterion
2 Posterolateral - Asterion
What is the last fontanelle to close after birth?
Anterior - between 1.5 - 2 yrs
-Derived from?
-How do they form?
-Neural crest ectoderm
-Intramembranous ossification
What part of the viscerocranium forms by endochondrial ossification? Which arch?
-Malleus/incus (Arch 1)
-Stapes/Styloid process (Arch 2)
What are the calvaria bones?
-Interparietal part of occipital
What are the first fontanelles to close?
Posterior and Anteriolateral
-2 to 3 months
What are the next fontanelles to close?
Posteriorlateral - 1yr
And last?
Anterior - 1.5 to 2 yrs
What is a Dysraphic malformation of the skull referring to?
Absence of calvaria bones, or an opening between them.
What is a severe form of Dysraphic skull?
Acrania - absence of the calvaria.
What are 3 defects related to sutures?
1. Craniosynostosis
2. Craniofacial Dysostosis
3. Cloverleaf skull
What is Craniosynostosis?
Premature closure of the sutures
What sutures do most Craniosynostoses involve?
-What sex is it more common in?
50% - sagittal
30% - coronal
More often in males
What defect is associated with Craniosynostosis?
Defective FGF Receptor 1/2 genes
What is the result of craniosynostosis?
Assymetric skull
What is Cloverleaf skull?
Severe form of craniosynostosis; Skull grows in 3 directions
What is a Dysraphic skull defect always associated with?
What is microcephaly?
Normal face, but small calvarium
-Assoc w/ defective cerebral hemisphere growth
What is an example of a Craniovertebral Junction defect?
Occipitalization of the Atlas
What are common features associated with craniovertebral junction defects?
-Short neck
-Low nuchal hairline
-Restricted movement of head on the spine
What could cause Craniovertebral Junction Defects?
Defective Hox signalling and regional patterning
What is Macrocephaly?
Enlarged skull due to excess bone thickness
Appendicular Skeleton consists of:
-Limb girdles
-Limb bones
Appendicular skeleton is derived from:
Somatic mesoderm
2 Anomalies of Pectoral girdle formation:
1. Cleidocranial Dysplasia
2. Sprengel Anomaly
What is Cleidocranial dysplasia?
Hypo or Aplastic Clavicles
What is Sprengel Anomaly?
High set scapula - hypoplastic
How do joints form?
1. Cartilages approach
2. Perichondrium forms and surrounds future joint
3. Interzonal mesenchyme differentiates
What 3 types of joints can form from Interzone Mesenchyme differentiation?
1. Fibrous
2. Cartilaginous (hyaline)
3. Synovial
What are the 2 components of Interzone mesenchyme in Synovial joints, what do they become?
1. Peripheral - becomes ligaments
2. Central - becomes synovial cavity.
What do skeletal tissue dysplasias affect?
What problem causes these?
-Growth in all/part of skeleton
-Abnormal extracellular matrix production
What does the term Chondrodystrophia describe?
A group of disorders characterized by disproportionate growth.
What is the most common chondrodystrophia?
Achondroplasia - the most common type of dwarfism.
What type of stature does a person with Achondroplasia have?
-Normal trunk
-Short limbs
-Large cranium, small face
What mutation is associated with Achondroplasia?
FGF Receptor 3 gene
Marfan Syndrome
-spidery long fingers
-aortic aneurisms
-joint hypermobility
-defect of Fibrillin prodctn
-Lysosomal storage disorder
-Chronic, progressive, multisystem deterioration
Osteogenesis Imperfecta
Collagen type I defect - brittle bones; respiratory problems
Which chondrodystrophia is not dominant inheritance?
2 Endocrine disorders that affect skeletal devo:
-Hyperpituitarism (too much GH)

-Hypothyroidism (Cretinism)
What is Gigantism?
-Rare form of hyperpituitarism
-If GH overproduction is prior to epiphyseal closure
What is the disease called if GH overproduction is AFTER epiphyseal closure?
What features are associated with Acromegaly?
Enlarged soft tissues and forehead
What age determines whether Acromegaly or Gigantism results?
-Prepuberty = Gigantism

-Postpuberty = Acromegaly
What are the common names for Hypopituitarism?
-Pituitary dwarfism
What symptoms result from cretinism?
-Mental retardation
-Skeletal/ear anomalies
-Younger bone age than actual age