Spine/Rib/Sternum and Limb Development Flashcards
What is the main progenitor tissue of the skeletal system?
**mesenchyme;
- paraxial mesoderm= vertebral column and ribs
- somatic mesoderm= sternum and limb skeleton
The vertebrae are formed from what type of cells?
Scleratome cells (beginning with somite number 5-6… The first 4-5 somites are termed the Occipital Somites and form basal portion of the skull)
Describe the process of resegmentation of scleratome subdivisions
- the cranial half of one somite merges with the caudal half of the next adjacent somite making vertebrae become intersegmental with respect to the original somite segmental pattern
- allows skeletal muscles (derived from dermomyotomes) to span adjacent vertebrae, intersegmental arteries to pass across the body of a vertebrae, and the spinal nerves to lie near the intervertebral discs
What is the importance of the scleratome subdomains?
Although the scleratome cells look similar under the microscope, they are organized into unique subdomains that form specific parts of the vertebrae (e.g. pedicle, body), intervertebral discs, ribs, tendons, and meninges
What influences the type of vertebrae formed at each level of the spinal column?
Axial patterning controlled by Hox genes and retinoic acid
When does ossification of the forming vertebrae occur?
- by week 8 there are 3-4 primary centers (2 per centrum, 1 per arch)
- closure of the neurocentral junction at 3-6 years
- secondary centers form at puberty
Describe the structure of a primitive vertebra
- Centrum (ventral)
- Pair of Neural Arches (dorsal).
- Costal and Transverse Processes will eventually extend from the arches
- thin layer of cartilage between the base of the neural arch and the centrum= Neurocentral Junction (a synchondrosis) **allows for growth of the vertebra in length from dorsal to ventral
Describe Klippel-Feil syndrome
- also called brevicollis
- rare recessive disorder characterized by the presence of several fused cervical vertebrae.
- the neck is shortened, there is a low nuchal hair line and limited cervical spine mobility
What are Sacralized/Lumbarized Vertebrae>
- Sacralization may occur if the fifth lumbar vertebrae is incorporated into the sacrum (4 lumbar, 6 sacral)
- If the first sacral vertebra is not included in the sacrum, this is called Lumbarization (4 sacral, 6 free lumbar)
- worse outcomes because of increased mobility
- The total number of vertebrae in the spine remains unchanged.
What is Dysraphism?
- a failure of fusion of the neural arches (spinous process) of a vertebra
- Rachischisis (Schisis = open spine) is a condition were many or all vertebrae have unfused spinous processes.
-
Spina Bifida is a term used to designate a series of conditions where one or a few adjacent vertebrae have unfused spinous processes.
- Spina Bifida Occulta is the mildest form (20% of all types of spina bifida) and is usually asymptomatic
- prevent with folic acid prenatal supplementation
Give 3 examples of misformed vertebrae
- Hemivertebrae (he remainder of a vertebra that did not form completely)
- Wedge-shaped Vertebrae
- Unsegmented Vertebral Bars
**all can create asymmetry in the spine leading to abnormal curvatures such as Scoliosis
What are Kyphosis and Lordosis?
conditions where there is an exaggeration of one of the normal curvatures of the spine. These may be congenital due to vertebral malformation or acquired
How do ribs form?
In the thoracic region of the spine, costal processes expand laterally forming the Ribs.
**sometimes things go wrong and people have accessory (more common in males by 3:1), fused, or forked ribs
How does the sternum form?
- primordia are derived from Somatic Mesoderm and begin independently as cartilage bars on either side of the midline during formation of the ventral body wall in the thorax
- the bars fuse and a secondary segmentation occurs forming several subsections
- refusion again forms the Body of the sternum. The cranial most segment/sternebra remains unfused and becomes the Manubrium while the Xiphoid Process forms at the caudal end
What is Pectus Excavatum?
- posterior depression of the sternum
- the heart may be pressed against the spine and deviated to the left
- surgery may be required to reduce the compression
- often an isolated anomaly
What is Pectus Carniatum?
- “keel-shaped” ventral protrusion of the sternum
- often an isolated anomaly with a prevalence in males of 4:1
What are limb fields?
Bilateral areas of somatic mesoderm at specific axial levels on the embryo that develop into the upper and lower limbs
**induced by Hox genes
What are limb buds?
- form for upper limb day 26-27; lower limb day 28-29
- core of Somatic Mesoderm covered by a jacket of Surface Ectoderm
- surface ectoderm forms a localized thickened ridge, the Apical Ectodermal Ridge (AER) that runs from anterior to posterior along the interface between the dorsal and ventral surfaces of the limb bud
**limb bud formation and axial position is inherent to the mesoderm
Describe limb elongation
- segments appear along a proximal-distal axis
- elongation results from epithelial-mesenchymal interactions at AER/mesoderm interface
- occurs around weeks 5-9
What are the three sets of linear axes along which limb development occurs?
- Proximal-Distal axis= limb outgrowth, elongation and segment formation
- Anterior-Posterior axis= digit development and development of cranial (preaxial) and caudal (postaxial) borders
- Dorsal-Ventral axis= compartment formation and muscle/neurovascular structure formation/subdivision
Describe development along the proximal-distal axis
- depends on inductive interactions between the AER (a signaling center) and underlying somatic mesoderm
- mesenchyme of the limb bud produces Fgf-10 which induces formation of the AER
- AER produces Fgf 8, 4 & 2, which maintain Fgf-10 production in the mesenchyme adjacent to the AER
- The mesenchyme adjacent to the AER continues to produce Fgf-10 which maintains Fgf 8 secretion by the AER until all segments of the limb are formed.
What happens if the AER is removed from the limb bud?
- Limb truncation/”amputation” along PD axis
- amelia (lack of limb)
- meromelia (partial limb development)
- Note: duplication of AER results in segment duplication/polydactyly
Describe development in the anterior-posterior axis
- digits develop in this axis
- preaxial (thumb) and postaxial (pinky finger) borders form
-
ZPA (zone of polarizing activity) along the posterior border of the limb signals to the mesenchyme to maintain digit formation
- sets up a focus of Hox gene expression
- sonic hedgehod (Shh) retinoic acid bead has the same effect
What are the possible malformations with failure of formation along the AP axis?
**amputation along the AP axis;
- meromelia (lacking of a part, but not all, of one or more limbs with the presence of a hand or foot)
- hemimelia (part or all of the fibular bone is missing)
- phocomelia (arm missing, hand articulates with girdle)
- oligodactyly
What is Syndactyly?
Complete or partial fusion of one or more digits
What is Sirenomelia?
- A more severe and very rare birth defect (in the category of syndactyly)
- may be the result of fused limb fields or perhaps abnormal development of the tailbud
Describe the development along the dorsal ventral axis
- DV axis influences skeletal muscles (myoblasts organize into dorsal and ventral premuscle masses)
- Also affects;
- neural and vascular structures
- limb compartmentalization
- Also affects;
- Mediators= Wnt-7a and transcription factor engrailed (En)
- form gradient that differentiates ventral and dorsal side
Describe developmental dysplasia
- congenital dislocation of the hip
- increased in females; feature of several syndromes
- under development of femoral head or hip socket and general joint laxity can occur
What is sprengel deformity?
- “undescended scapula” is characterized by a scapula that is located at C4-T2 (normal is T2-T7), and is dysplastic
- muscles associate with the scapula are hypoplastic or atrophic limiting shoulder movement and causing disfigurement
What is Cleidocranial Dysplasia?
- hypoplasia (decreased size) or aplasia (absence) of the clavicles
- phenotype similar to RunX2 heterozygotes
