Blake_Anatomy_11_Development of Musc Skel Flashcards
Axial Skeletongenesis (2)
- vertebrae form as an intersegmental structure derived from adjacent sclerotomes
- Sclerotomes split into cranial (rostral) and caudal sections
Skeletogenesis of the Vertebral Column (4)
- Caudal portion of one sclerotome fuses with cranial portion of the sclerotome caudal to it
- Vertebra are intersegmental
- Spinal nerves emerge between the vertebrae and grow out to contact myotome
- Originally 8 cervical somites =>8 spinal nerves
- Fusion results in 7 cervical vertebrae (Occipital Bone is formed from O4 and C1 sclerotomes)
- Cervical spinal nerves exit above vertebra
- other spinal nerves exit below vertebra
Skeletogenesis: Vertebral Column
- Sclerotomes form _________ surrounding the developing spinal cord
- Also form __________ (centrum)
- What happens to the notochord?
- neural arches
- vertebral body
- The notochord regresses except where it is incorporated into the intervertebral discs
What is a herniated disc?
Nucleous pulposus is herniateing into the spinal canal. Thus compressing a spinal nerve.
Congenital Scoliosis
- Definition
- Types
- Abnormal lateral curvature of the spine, resulting from disruption of normal vertebral development. Abnormal formation or segmenting of somites.
- Types
- Failure of formaiton (Hemibertebrae; aka “wedge”)
- Failure of segmentation (Unsegmented Bar)
- Mixed (Unsegmented with Hemivertebrae)
Neurofibromatosis
- NF1/NF2 - nervous disease
- NF1 most common
- accompanied by orthopedic problems such as scoliosis
http://www.webmd.com/pain-management/neurofibromatosis
- often NF1 is accompanied by scoliosis
Formation of Vertebrae and Ribs
- Ribs arise from zones of condensed mesenchyme lateral to the body of the vertebra (from the sclerotome)
- Ribs develop from costal processes, grow into ribs in throracic region
Deformations of Vertebrae and Ribs
Lumbar and Cervical ribs - can be complete but usually a rudimentary process
Skeletogenesis: Sternum
- Develops from cartilaginous sternal bars in ventral body wall
- Fuse with one another in cranial caudla diriction
- forms a Manubrium body and Xiphoid process
Defects of the sternum (5)
- Pectus excavatum
- Petus carinatum
- Sternal cleft
- Sternal foramen
- bifid xiphoid
Pectus Excavatus
- Causes
- Outcomes
- Frequency
- P.E. caused by overgrowth of costal cartilage Cause unknown
- Restricts the expansion of the ribs and pushes the sternum inward
- 1 in 500-1000 children; 3x males
Pectus Carinatum
Overgrowt of cartilage causing the sternum to protrude. can be evident at birth; or ESP in adolescent males during growth spurt. It may occur as a solitary congenital abnormality or in association with other genetic disorders or syndromes
Sternal Foramen (4)
- Ossification anomaly found in 4-10% of population
- Can be mistaken for a bullet wound or sternal disease by CT scan
- Common acupuncture point
- directly over the heart
Appendicular Skeletogenesis: intro (4)
- Very complex patterns of Hox gene expression
- Inductive interactions between mesoderm and ectoderm (epithelia)
- Mechanical infuences (early morphogenesis - late prenatal)
- Anomalies - common and highly visible, may be ralated to disturbances in specific cellular or molecular interactions
Initiation of limb development (3)
- Outgrowth of body wall late in week 4, FL>HL
- Positioning of the limbs along the craniocaudal axis is regulated by Hox genes expressed along this axis
- Expressed in overlapping patterns from head to tail
Limb growth in other axes: (2)
- Once positioning along the craniocaudal axis is determined, growth must be regulated along the proximodistal, anteroposterior, and dorsoventral axes.
- Limb outgrowth is initiated by TBX5 and FGF10 in the forelimb and TBX4 and FGF10 in the hindlimb secreted by lateral plate mesoderm cells.
TBX4 and TBX5
TBX5 upper limb
TBX4 lower limb
Types of Reduction defects (3)
Arrest or failure of development
- Meromelia - part of limb missing
- Amelia - all of limb is missing
- Phocomelia - feet and hands arise close to the trunk
- (phocid = animals with flippers)
Meromelia
part of limb is missing
Mesomelia
Shortened forearm or leg elements
Radial Club hand
- congenital absence or hypoplasia of the forearm structure and hand
- Hypoplastic or absent muscular structures and radial nerve
- Treatment is best if early: passive stretching exercises and corrective casting
AER
Apical Ectodermal Ridge
Formation of the AER
- Once limb outgrowth is initiated, BMPs, expressed in the ventral ectoderm, induce formation of the AER
- The AER signals limb growth from the Hox gene
Organization and Polarity of the Developing Limb Bud
- Limb Bud has a strict pattern and polarity
- development is organized around three axes
- Limb tissue differentiation is now controlled by 2 regions:
- Apical Ectodermal Ridge (AER)
- Zone of polarizing activity (ZPA)
- Also the progress zone (PZ) where mitosis and limb lengthening occur
Limb Patterning: Axes
- AER - thickened ectoderm on apex of limb bud
- Directs limb bud organization along proximo-distal axis
- Maintains dorsal/ventral axes
Or:
AER Regulates growth from proximal to distal identifies dorsal and ventral axes
Outgrowth of the limb (2)
- After AER is established it expresses FGF4 and FGF8, whch maintain the progress zone (PZ= the rapidly proliferating populaiton of mesenchyme cells adjacent to the ridge)
- Distal growth of the limb is then affected by these rapidly proliferating cells under the influence of the FGFs
ZPA
Zone of polarizing activity
- Mesodermal cells located at the base of the limb bud
- Produces retinoic acid which initiates expression of SHH
- Directs organization of limb bud and patterning of digits
- Misexpression of Retinoic acid or SHH results in a mirror image duplication of the limb structures
- Determines anterior (preaxial/thumb), Posterior (postaxial)
Duplication defects
- description
- 2 causes
- Duplication of complete limbs, partial limbs or digits
- Misexpression of RA and/or SHH (over expression)
- Duplication of AER (extra or split)
Polydactlyly (5)
- Common
- Often extradigit is incompletely formed and useless
- Extra digit is commonly medial or lateral rather than central
- In a foot, the extra digit is usually lateral
- Dominant trait
Segmentaion of limb buds
- Limb grows and develops proximo-distally
- Zone of Cell Division (PZ) = region of activily dividing cells
- Zone of Differentiation: region of cell specialization
How are the type/shape of bones regulated?
Hox genes
forelimb: HoxD 5’
How does the proximal/distal position of cells relate to the AER?
- AER secretes FGFs that influence the closest cells (PZ) to development into distal structures
- Cells no longer within range of AER remain proximal in nature.
Why does Thalidomide produce Reduction defects?
Thalidomide disrupts FGF4 signaling from the AER to the PZ
How are digits differentiated during development
- Day 48: Apoptosis in the apical ectodermal ridge creates a separate ridge for each digit
- Day 51: apoptosis of interdigital spaces produces separation of the digits
- Day 56: digit separation is complete
Syndactyly
- Most common limb abnormality
- webbed fingers or toes
- failure of programed apoptosis in digital ray
- More frequent between 3rd and 4th fingers and 2nd and 3rd toes
- Simple dominant or Simple recessive inheritance
Bradydactyly
- Short Digits
- Uncommon
- Reduction in lenght of phalanges
- Dominant trait
- Short stature
Cleft Hand or Foot
- Uncommon
- Lobster-Claw
- Absence of one or more central digits or between digits 2 and 4
- Cleft hand or foot is divided into 2 parts that oppose each other
- Remaining digits are partly or completely fused
Contribution of Embryonic Cells to the developing limb bud
- Lateral Plate Mesoderm
- Hypaxial Mesoderm
- Neural Crest
- Neural tube
- Lateral Plate Mesoderm - skeleton and vasculature
- Hypaxial Mesoderm - muscles
- Neural Crest - schwann cells
- Neural tube - motor/sensory axons (dermatome map)
Other congenital limb anomalies (4)
- Etiology unknown
- Probably multifactorial - interactions between genetics and environment
- Complex and interactive nature of limb development
- Grouped as reduction defects, duplication defects, and malformations
Malformations (4)
- Overgrowth
- Undergrowth
- Focal Defects
- Associated with other general/syndromic skeletal abnormalities
Sirenomelia
- “mermaid syndrome”
- Types I-VII classified by degree of fusion
Sirenomelia Intervention:
- Legs are fused together by skikn and feet splayed in V-shape
- Saline sacks inserted and gradually filled to stretch the skin
- Two operations, three months apart, separate the leges, using the stetched skin to cover the wounds
- Later operation will rotate splayed feet forward.
Achondroplasia (5)
- Most prevalent form of dwarfism
- Mutation on FGF-R3
- Pathologic changes at ephiphyseal plate; Zones of Proliferation, and Hypertrophy are narrow and disorganized.
- Autosomal Dominant
- Failure of proliferation and column formation of epiphyseal cartilage cells (defect in endochondrial bone formation which impairs longitudinal growth of tubular bones)
Osteogenesis Imperfecta (4)
- Brittle bone disease
- Bone fragility that predisposes to fractures and deformities related to connective tissue abnormalities
- Blue Sclera
- Not alway evident at birth
Talipes Equinovarus (4)
- Club Foot
- Most common type
- 1/1000 births; 2x in males
- Sole of foot turned medially and foot is inverted
2 types of Club foot
- Flexible
- Results from abnormal positioning or restricted movement of lower limbs in utero
- feet are structurally normal
- Usually autocorrect spontaneously
- Rigid
- Abnormal developmet of the ankle and foot joint during weeks 6-7
- bony deformities, particularly in the talus
Treatment of Talipes Equinovarus
Over 2-3 months, on a daily basis corrective devices are systematically revolved into proper position.
Rotational Abnormalities
Different from club foot
