Development of the MSK Flashcards
What cells form the paraxial mesoderm?
Cells derived from the primitive node
Paraxial Mesoderm
Thick, bilateral longitudinal columns of cells along the developing NT
Each column of paraxial mesoderm is continuous with ___ mesoderm which gradually thins into a layer of ___ mesoderm
- Intermediate
- Lateral (plate)
Lateral (plate) mesoderm is continuous with ____ mesoderm
Extraembryonic
Extraembryonic mesoderm covers the:
Umbilical Vesicle & Amnion
What mesoderm type forms on either side of the notochord?
Paraxial mesoderm (next is intermediate mesoderm then lateral plate mesoderm)
When do the paraxial mesoderm differentiate, condense and form paired somites (form in head to tail/craniocaudal fashion)?
End of the 3rd week
Where do the fist somites form?
In the future occipital region
How many somites develop initially?
38-39 pairs
How many somite pairs form by the end of the 5th week?
42-44 pairs
Shortly after forming, each somite pair separates into __
subdivisions
Ventromedial part of somite undergoes EMT and forms the:
Sclerotome
Dorsal part of somite forms __ which further divides into __ and __
- Dermamyotome
- Dermatome & Myotome
Intermediate part of somite forms ___
Syndetome (located between sclerotome and myotome)
Central Sclerotome:
- Pedicles
- Ventral parts of neural arches
- Transverse processes
- Proximal ribs
Ventral Sclerotome:
Vertebral body
Dorsal Sclerotome:
- Vertebral arch
- Vertebral spine (spinous process)
- Lamina of the vertebral arch
Lateral Sclerotome:
Distal ribs
What are the two parts of a sclerotome that divide? Which parts of the divided sclerotome combine?
- Cranial and caudal parts with a intersegmental boundary between (somitocoele cells, von ebners fissure)
- The caudal part of the superior sclerotome combines with the cranial part of the inferior sclerotome to produce vertebrae
How are the cells organized in the cranial part of the sclerotome? Caudal part?
- Cranial portion contains loosely packed cells
- Caudal portion contains tight/densely packed cells
Where is the nerve initially trying to grow out before sclerotome resegmentation occurs?
At the intrasegmental boundary
Why does the sclerotome undergo resegmentation? What does resegmentation this explain?
- Because the migrating NCC and axons of the motor neurons can only migrate towards the cranial portion of the sclerotome; allows us to have the range of muscle actions that we do for many of our vertebral muscles
- This explains why there are 8 cervical nerves but only 7 vertebrae, and also why the C1 nerve comes out above its cervical vertebrae
What mediates resegmentation?
Protein signaling
What contributes to formation of the occipital bone of the skull?
Cranial half of the C1 sclerotome fuses with the sclerotome superior
How many vertebrae do muscle masses span?
2
What do ribs develop from?
Costal Processes of the thoracic vertebrae
Ribs are cartilaginous during the ___ period and go through endochondrial ossification during the ___ period
- Embryo
- Fetal
What part of the sternum is the last to ossify and sometimes remains cartilaginous for entire lifetime?
Xiphoid Process
When do ribs start forming?
35 days / 5th week of development
Paired sternal bars arise in the body wall from somatic layer of ___ ___ ___
Lateral Plate Mesoderm
Sternum Development
(1) Paired sternal bars arise in body wall from lateral plate mesoderm
(2) Originally ventrolateral but move medially
(3) Fuse in a cranial-caudal manner to form cartilaginous models of the manubrium, sternebrae, and xiphoid process
What ribs grow faster, true ribs or false/floating ribs?
True ribs
What gene codes for vertebrae identity?
Hox genes
What gene is important at the thoracic/lumbar boundary?
Hox10 (presence of this gene leads to the loss of ribs that is seen in the lumbar region, not the thoracic region)
Hox Genes
- Different Hox gene families expressed in different segments of the vertebrae
- Family members have nested pattern of expression boundaries along cranial-caudal axis
- Boundaries correspond to changes in vertebral shape – changes in expression causes transformations of vertebrae
What happens if there is a loss of Hox10 paralogs?
Leads to presence of thoracic vertebrae/ribs growing in the lumbar and sacral region
What happens if there is a gain of Hox10 paralogs?
Leads to loss of ribs in the thoracic region; what was supposed to be thoracic vertebrae is now lumbar vertebrae
Where do intervertebral discs develop?
At the intrasegmental boundary (between cranial and caudal segments of the sclerotomes that make the vertebrae)
What is the core of each intervertebral disc composed of?
Notochordal cells that produce the Nucleus Pulposus
What does the annulus fibrosis (surrounds the nucleus pulposus) develop from?
Somitocoele cells
Notochord DOES NOT directly contribute to the vertebrae but remnants can give rise to rare tumors called:
Chordomas
What is myogenesis?
The process where myogenic precursors (myotomes) undergo EMT to form skeletal muscle of the trunk and limbs
List the steps of Myogenesis
(1) Elongation of nuclei and cell bodies of mesenchymal cells -> differentiate into myoblasts
(2) Myoblasts fuse to form myotubes (elongated, multinucleated, cyndrical structures)
(4) During/after fusion, myofilaments develop in the cytoplasm of the myotubes – become invested with connective tissue to produce fasicles
Genes expressed when myogenic precursors are in quiescence
- PAX7
- PAX3
- MYF5
Genes expressed when myogenesis is activated
- MYOD1
- MYF5
- PAX 3/7
Genes expressed during the differentiation phase of myogenesis
- MYOD1
- MYOG
- MYF6
Most skeletal muscles develop before __
Birth (almost all remaining muscles are formed by the end of the first year)
Where are myotomes located?
Along each segment of the trunk, cranial-to-caudal (occipital, cervical, thoracic, lumbar, ect)
What are the 2 segments the myotome divides into?
- Epimere (dorsal/posterior)
- Hypomere (ventral/anterior)
What does the Epaxial division form?
- Extensor muscles of neck and vertebral column (erector spinae, transverse spinalis muscles)
What does the Hypoaxial division form?
- Hypaxial muscles of the lateral and ventral walls in the thorax and abdomen
- Limb muslces
What are the 4 different myotomes of the Hypaxial Division?
- Cervical myotomes: scalene, prevertebral geniohyoid and infrahyoid muscles
- Thoracic myotomes: lateral and ventral flexor muscles of the vertebral column
- Lumbar myotomes: quadratus lumborum
- Sacrococcygeal myotomes: pelvic floor musculature, striated muscles of anus and sex organs
Developing spinal nerves divide into what 2 ramus to innervate trunk musculature? What muscles do they supply?
- Dorsal ramus: supplies epaxial muscles
- Ventral ramus: supplies hypaxial muscles
Tendons connecting muscle and vertebrae arise from the:
Syndetome (region of somite between developing sclerotome and myotome)
What forms primitive axons and enters skeletal muscle of the body wall?
Motor neuroblasts
What day does the myotome split into two different segments?
Day 40
When is the layout of the myotomes complete?
Day 50
Dermatome Definition
- Area of skin innervated by one single spinal nerve or spinal segment
- Associated with posterior root
Myotome Definition
- Muscles innervated by one single spinal nerve or spinal segment
- Associated with anterior root
What are the 5 skeletal wall malformations?
- Cervical ribs
- Pectus Excavatum
- Pectus Carinatum
- Poland Syndrome
- Prune-Belly Syndrome
Cervical Ribs
- Typically attached to C7
- 1% of population
- May impinge on brachial plexus and/or subclavian artery (thoracic outlet syndrome)
Pectus Excavatum
- 1/300 to 1/400 births
- Depressed sternum, sunken posteriorly
- “Funnel chest”
- Can impinge on lung function
Pectus Carinatum
- 1/1500 to 1/2000 births
- Protrusion of the sternum and costal cartilages
- “Pigeon chest”
Poland Syndrome
- 1/10,000 to 1/100,000 live births
- Encompass a constellation of anomalies
- Partial (28%) or complete (72%) absence of pectoral muscles
- Most commonly unilateral
- Associated anomalies include: Aplasia/hypoplasia of other chest wall muscles/breast/nipple, absense of teh costal cartilages of ribs 2-4 or 3-5, high-riding scapula (Sprengel deformity), digital anomalies
Prune Belly Syndrome
- Congenital disorder defined by a characteristic clinical triad:
(1) partial or complete absence of abdominal musculature (mesodermal malformation)
(2) Cryptorchidism (failure of one/both testes to descend)
(3) Malformation of urinary tract and bladder/urethral obstruction - fluid accumulation distends the abdomen causing muscle atrophy, display concomitant cardiopulmonary, GI and MSK anomalies
- very rare
- 20% of children are stillborn and 50% do not survive to 2yrs