Skeletal System Development Flashcards
How is the neural crest induced?
Interaction between the neural plate and ectoderm, with signal emanating from the ectoderm and received by neuroepithelium, although some signalling does go the other way
What is the function of mesoderm and neural crest cells in the head and neck?
They contribute to make mesenchyme, which produces many cell types including fibroblasts, osteoblasts, and chondroblasts, and will form bones + cartilage by these
What germ layer forms the vertebral column + ribs?
The sclerotome
What induces the sclerotome?
The neural tube, it tells it to produce vertebrae and intervertebral discs.
It is also induced by notochord by release of sonic hedgehog (Shh)
What forms the vertebral arch?
Sclerotome surrounding the neural tube
What forms the centrum?
Sclerotome surrounding the notochord. The centrum is the promordium of the vertebral body
What forms the two sections of intervertebral discs?
sclerotome surrounding the notochord makes anulus fibrosis
Notochord makes nucleus pulposus
What forms the costal process?
Remaining sclerotome after formation of centrum and vertebral arches. This will form the ribs
How is a vertebral body formed by sclerotome?
Sclerotome divides into two things:
Anterior sclerotome - loosely packed
Posterior sclerotome - densely packed
Densely packed sclerotome of the cranial somite will combine with loosely packed sclerotome of caudal somite to form vertebral bodies. The notochord degenerates in these areas and is in the intervertebral discs.
How do vertebral arches form by sclerotome?
they are formed by a single somite, unlike vertebral bodies
What happens to the sclerotome cells in the middle of each somite (between anterior and posterior sclerotome)?
They form the annulus fibrosis, around which the segmental nerve travels to the the corresponding segmented somite
Why are there 7 cervical vertebrae from 8 somites (and thus 8 cervical nerves)?
Anterior sclerotome of first somite forms part of occipital bone, while the posterior sclerotome forms the cranial portion of the first vertebral body.
Posterior sclerotome of last somite forms the vertebral body of T1
When does the cartilage of the vertebrae start to form? When does ossification start?
Forms from mesenchyme starting from week 6. Ossification begins in weeks 7-8 and continues to 25 years or so.
What are the three primary ossification centers of the vertebrae?
- The centrum (circular around notochord)
2/3. One for each half of vertebral arch (in pedicle region)
What are the cartilaginous joints of the vertebrae? What are they
They are the cartilage of the vertebrae which has not yet at birth. This allows for expansion of spinal cord during growth. There are 3 of them:
1/2. Between centrum bone and each half of vertebral arch bone (around pedicle)
3. The vertebral arch joint, between halves of vertebral arch bone
When do the arches fuse to the centrum?
By 3-6 years they have ossified, this is postnatal ossification
What are the secondary ossification centers of the vertebrae?
Tips of spinous and transverse processes, as well as the annular epiphysises of vertebral bodies
What is spina bifida? What can cause it?
The failure of a vertebral arch to fuse. It is mainly caused by folic acid insufficiency
What is spina bifida occulta?
Most mild form of spina bifida. Site is covered by skin and marked with a tuft of hair, insignificant but prone to trauma
What is spina bifida cystica?
Spina bifida involving herniation of meninges and/or spinal cord through defect in vertebral arch. It is covered by skin or thin membrane which occurs most commonly in lumbar region
What is a meningocele?
A form of spina bifida cystica, it is when meninges and CSF protrude but not the spinal cord
What is a meningomyelocele?
A form of spina bifida cystica, when meninges AND spinal cord are in cyst. Usually pretty bad with loss of function
What is rachischisis?
Most severe form of spina bifida cystica - lethal. It is a series of wide open vertebrae associated with open neural tube, when neural folds don’t close.
What is hemivertebra?
When primary chondrification center does not appear on one side of centrum, producing only half a vertebral body. Causes scoliosis -> lateral curvature of spine
What are true vs false ribs, and what are the floating ribs?
Ribs 1-7: True ribs which have cartilages connecting directly from sternum
Ribs 8-10: False ribs which have cartilages connecting to the 7th rib cartilage
Ribs 11-12: Floating ribs which do not connect to the sternum and are not the size of full ribs
How does the sternum develop?
Two vertical bars of mesenchyme called sternal bars. They move medially and fuse at midline to form the manubrium, sternebrae, and xiphoid process
What is the purpose of the sternebrae?
There are 6 of them, segmenting the sternum. Bottom one is the xiphoid process and does not ossify until late in life. The cartilage between them allows for vertical growth.
What are accessory ribs?
An inappropriate presence of costal process in cervical or lumbar region. Usually asymptomatic when at the cervical level, but may interfere with brachial plexus or subclavian artery
What is a bifurcated rib?
When the sternal end of the rib is cleaved into two
What is a cleft sternum?
When the sternal bars fail to fuse
What induces the skull?
Inductive influence of brain on surrounding mesenchyme
What is the neurocranium vs viscerocranium?
Neuro: Protective case for brain
Viscero: Skeleton of face (made by mostly neural crest)
By what process do both neurocranium and viscerocranium form?
Both have membranous parts formed by IO
Both have cartilaginous parts formed by EO
What is the membranous neurocranium?
Formed by intramembranous ossification, they are the flat bones of the calvarium including frontal, parietal, occipital, and squamous part of temporal bones.
What two things bridge the membranous neurocranium?
Sutures - dense connective tissue which allows for molding of skull around growing brain
Fontanelles - six large membranes where the sutures meet
The sutures close in adulthood by ossification, and the fontanelles close by the end of year 2 of life
What are the 6 fontanelles?
Anterior, posterior, 2 anterolateral (sphenoidal), 2 posterolateral (mastoid)
What is the cartilaginous neurocranium?
Base of skull is formed by fusion of cartilages
What forms the cartilaginous viscerocranium?
Derived from first pharyngeal arch cartilage
What is an example of membranous viscerocranium?
Most of the mandible is not derived from cartilage
What is meningocele vs meningoencephalocele vs meningohydroencephalocele?
Meningocele - meninges herniates through opening in skull
Meningoencephalocele - meninges and brain tissue herniates through opening in skull
Meningohydroencephalocele - meninges, brain tissue, and ventricle portion herniates through opening in skull
What is acrania? What characterizes it?
Failure of calvaria and prosecephalon to form. Failure of rostral neuropore to close. It is the most common anomaly in stillborn infants, infants usually die within hours.
Characterized by alphafetoprotein elevation in amniotic fluid and polyhydramnios (since fetus lacks CNS control to swallow amniotic fluid)
What is craniosynostosis?
Premature closure of skull sutures producing unusual shapes of skull - defect depends on sutures affecting
What is microcephaly?
Failure of brain to grow which may reduce growth of skull via less inductive interaction from neuroepithelium of brain (i.e. Zika babies)
When do limb buds appear?
By about the 4th week, upper limb starts developing about two days before lower limb
What is the AER?
Apical ectodermal ridge - thickened portion of ectoderm at tip of limb bud inducing growth and differentiation of limb mesenchyme by secretion of fibroblast growth factor (controls the proximal / distal axis of the limb)
What gives rise to the limbs?
The somatopleure from lateral mesoderm, it gives rise to the appendicular skeleton. Remember that it’s the lateral somite that gives rise to the voluntary muscle
What is the ZPA?
Zone of polarizing activity - organizes limb along the anterior-posterior axis by extending lengthwise from proximal to distal on the posterior side of limb bud (will make a pinky). It expresses sonic hedgehog, influenced by fibroblast growth factor (from AER) and retinoic acid (from vitamin A, HOX gene sensitive)
What is the PZ?
The PZ - zone of mesenchyme behind the AER which makes the skeleton as the limb grows. It expresses specific HOX genes and is dependent on the amount of FGF from AER and Shh from ZPA to know where it is supposed to grow.
How are cells induced in the progress zone?
FGF from AER binds to FGF receptor (a receptor tyrosine kinase). RTK then phosphorylates critical proteins, inducing retinoic acid acid release. Retinoic acid induces HOX gene expression in target cells
How is the pattern of the limb skeleton directed?
39 HOX (HomeOboX) genes distributed into 4 linkage groups, induced by retinoic acid from FGF diffusion from AER in a topological pattern.
What does the limb formation cause in the mother?
Increased demand on maternal calcium and phosphorus
When do the primary and secondary centers of ossification form?
Primary - in diaphysis prenatally.
Secondary - in epiphysis postnatally.
Bone grows in epiphyseal cartilage plate until about 20 years
How is the webbing of digits removed?
Via apoptosis. Thumb will be pointed up and requires lateral rotation
What are amelia and meromelia?
Amelia - complete absence of limb, normally by affecting AER expression (as in thalidomide babies)
Meromelia - Partial absence of limb
What is clubfoot?
Also called talipes, deformity of foot involving ankle bone. Kid walks on ankle and not foot because foot is mispositioned
What is syndactyly vs polydactyly
Syn - Fusion of digits
Poly - extra digits (too much apoptosis
Syndactyly may be cutaneous (less serious) or osseous (more serious, where bone is fused)
What is achondroplasia?
Most common cause of dwarfism (shortness of stature)
- trunk is normal length, but limbs are short due to disturbance of epiphyseal plate
What is hyperpituitarism? What can it cause?
A condition which can lead to excessive secretion of growth hormone which can cause giganticism (Rapid / excessive growth) or acromegaly (epiphyseal and diphyseal centers fuse post-childhood so the bones cannot elongate, but visceral organs, soft tissues, and bones of face hands and feet grow)
What is hypothyroidism / cretinism?
Deficiency in fetal thyroid hormone, causes growth retardation, skeletal abnormalities, mental deficiency, auditory and neurological disorders
