Download Recognize bone formation through intramembranous and

Lecture 2: Embryology of Bone and Muscle I
Reading Reference: Sadler, pp. 133-161
Learning Objectives
1. Recognize bone formation through intramembranous and endochondral ossification.
a. Intramembranous ossificationi. Forms the flat bones of the skull from mesenchymal cells ( neural crest or paraxial mesoderm
,specifically sclerotome).
ii. Starts when the embryo is 7 weeks old and continues until birth
iii. The primary ossification centers in the formation of flat bones are the eminences
iv. Process:
1. Mesenchymal cells aggregate with connective tissue to form a membrane
2. They deposit osteoid (unmineralized bone) and become osteoblasts
3. Osteoblasts secrete calcium matrix and become trapped in it and become osteocytes
4. Mesenchymal cells nearby become periosteum
5. Osteoclasts degrade the matrix to form the spongy bone
v. CLINICAL SIGNIFICANCE:
1. failure of skull to form completely causes meninges to herniate (cranial meningocele or
encephalocele if brain tissue is involved)
2. craniosynostosis- premature fusion of fontanelles at sutures  deformed head
b. Endochondral Ossificationi. Forms remaining bones (basicranium and post-cranial bones) from somatic lateral plate
mesoderm
ii. Starts at 5 weeks and continues until birth
iii. Process:
1. Mesenchymal cells aggregate and differentiate into chondrocytes
2. Chondrocytes hypertrophy while producing alkaline phosphate (calcifies the matrix)
3. The remaining cells make the periosteum
4. A bony collar forms from the periosteum where a blood vessel penetrates and brings with
it osteoclasts (since they are derived from blood cells) and osteogenic cells
5. Osteogenic cells differentiate into osteoblasts/osteocytes and form spongy bone
(PRIMARY ossification center)
6. Spongy bone is repeatedly deposited and resorbed
7. Because of chondrocyte death and osteoclast activity, marrow cavity forms
8. After the diaphysis, the process repeats itself into the epiphyses which is the SECONDARY
ossification center
9. This continues to happen until the only cartilage we are left with is articular cartilage
(cushions joints) and the epiphyseal plate (important for bone growth)
2. Recognize formation of the cartilaginous and bony vertebra from the sclerotome.
a. Sclerotome (derived from paraxial mesoderm) gives rise to the vertebrae and the annulus fibrosus portion of
IV disc
b. Sclerotomal resegmentation:
i. sclerotomal cells on the lower side of the upper somite migrate inferiorly and medially.
ii. Sclerotomal cells on the upper side of the lower somite migrate superiorly and medially
iii. The migrating sclerotomal cells fuse
iv. Sclerotomal fissure: where one somite divides into an “upper” and “lower” part that migrate in
opposite directions
v. The separation of the sclerotomal cells create a space where spinal nerves emerge
vi. The nerves that emerge connect to the embryonic myotome which differentiates into muscle and
then migrates to their final position in the body
vii. Development of IV disc:
1. Sclerotomal cells surround the notochord which will die where the sclerotomal cells come
together to form the vertebral bodies but persist in the area in between and form the
nucleus pulposus of the IV disc
2. The sclerotomal cells will then form the annulus fibrosus
3. CLINICAL SIGNIFICANCE:
a. IF notochord cells don’t die in the region where sclerotomal cells come together, get
a fatal cancer called Chordoma (usually at the sacrum or cranial base)
3. Recognize malformations of the vertebra: hemivertebra, spondylolisthesis, spina bifida,
congenital kyphosis and lordosis.
a. Hemivertebra- results from Scoliosis which is lateral curvature that happens due to unequal distribution of
sclerotomal cells from somites on either side of the embryo. Obvious during growth spurts.
b. Spondylolisthesis- when a vertebra is displaced in the forward direction, especially L5. Can be congenital
(more prone to slipping of vertebrae)
c. Spina bifidai. due to incomplete formation of vertebral laminae (as opposed to rachischisis, due to failure of
caudal neuropore of the neural tube to close)
ii. cells migrating around the spinal cord won’t migrate all the way around and fuse and we are left with
a piece of bone on each side: bifid process, hence the name spina bifida
iii. SB occulta: hidden, asymptomatic, usually one vertebrae involved, patch of hair is common
iv. SB meningocele: more vertebrae involved but no nervous tissue involvement
v. SB myelomeningocele: involves both the meninges and neural tissue
d. Congenital kyphosis and lordosis: failure of vertebrae to form in the proper anterior/posterior dimensions
4. Recognize formation of ribs.
a. Sclerotomal cells migrate along body wall and form costal processes that grow, in the thoracic region and
give rise to ribs.
i. Note: all our vertebrae form ribs but they just don’t grow all the way around.
1. The costal processes of the cervical vertebrae fuses with the transverse process and makes a
foramen
2. The costal processes of the lumbar vertebrae fuses with the transverse process and forms a
larger transverse process
3. The costal process of the thoracic vertebrae become the ribs and there is a region of cell
death where we get a costal facet. Make 2 bones out of 1.
4. The costal processes of the sacral vertebrae becomes the ala
b. By 45 days, the true ribs connect to the sternum which comes from lateral plate mesoderm
5. Identify malformations of the ribs, including supernumerary (or accessory) ribs and fused
ribs.
a. Supernumerary ribs- an extra rib may form in the cervical region and is called cervical rib. It will impinge
nerves and cause pain/numbness
b. Fused ribs- this happens if sclerotomal cells that are migrating fuse with sclerotomal cells of adjacent
somites. Also called costal synostosis. Can also get a bifid rib. Fused ribs lead to breathing difficulties.
6. Recognize formation of the sternum.
a. Somatic lateral plate mesoderm forms sternal bars- at day 43
b. Sternal bars fuse craniocaudally to form the sternum- at day 45
c. Cells of the sternal bars differentiate segmentally to form sternebrae (chondrocytes)- at birth
d. One or two ossification centers form in each sternabra. Can go on until age 40
7. Identify malformations of the sternum.
a. Sternal cleft- incomplete fusion of sternal bars
b. Sternal foramen- incomplete fusion of the ossification centers of the sternabra
c. Pectus Excavatum- overgrowth of ribs push the sternum posteriorly. May affect the heart
d. Complete absence of sternum- don’t confuse with sternal cleft- here we don’t get a sternum at all
8. Skeletal Muscle anatomy:
a. Muscles cells are long and extend the length of the muscle
b. Multinucleated (because multiple cells fused)
i. Cells that did not fuse are called satellite cells- serve as muscle stem cells that repair damages as
needed
c. Nuclei pushed out to the periphery
d. Cylindrical shape
9. Skeletal muscle Development:
a. Myotomal cells migrate dorsally and ventrally and become myoblasts
i. Ones that migrate dorsally: aggregate to form epimere which form epaxial muscles (true back
muscles)
ii. Ones that migrate ventrally: aggregate to form hypomere which form hypaxial muscles (muscles
of neck, limb, diaphragm)
b. Myoblasts fuse and form myotube
c. More fusion and growth occurs to form muscle fiber
d. Cells that don’t fuse become satellite cells.
10. Problems with muscles:
a. Note: variation in muscle among people is normal but it becomes a problem when it’s a major muscle
b. Poland Anomaly- unilateral absence of pectoralis major. More common in males on Right side.
c. Prune Belly syndrome- abdominal wall muscles don’t form. More common in males.
11. Limb Development:
a.
b.
c.
d.
Form from Ectoderm (skin part) and Lateral plate Mesoderm (everything else)
Growth in 3 dimensions: proximal-distal, medial-lateral, dorsal-ventral
IF limbs are developed, we are in the fetal stage not embryonic stage
Apical ectodermal ridge: when the limb bud initially grows out and flattens.
12. Proximal Distal Growth:
a. Ectodermal ridge tells mesodermal cells to divide (they are called progress zone cells)
b. Progress zone proteins secrete proteins that keep the ectodermal ridge cells alive
c. As the limb grows, progress zone cells are left behind, stop dividing, and start to differentiate into skeletal
components of limbs
13. Medial-Lateral Limb Growth:
a. Cells called zone of polarizing activity induce asymmetry in mature limbs and gives us the different types
of digits
b. Having additional ZPA causes digit duplication!
c. We don’t have fused fingers because there is apoptosis between our digits
14. Limb Abnormalities: (due to teratogen exposure usually like thalidomide)
a.
b.
c.
d.
Amelia: complete limb loss
Meromelia: partial limb loss
Polydactyly: extra digits
Syndactyly: fused digits