Dr. Cole's Development of the Skeletal System Flashcards
What are vertebrae derived from?
sclerotomes
Sclerotomes do what in the formation of vertebrae?
They split into caudal and cranial sections
What parts of the developing vertebrae fuse, and from what?
Sclerotomes divide into cranial and caudal parts, and the cranial parts fuse with the caudal part from the sclerotome adjacent to it.
During vertebrae development, what is happening with spinal nerves?
they are growing out between the newly forming vertebrae and merging with myotomes
Explain why there are 8 somites originally in the cervical region but only 7 cervical vertebrae
the sclerotomes divide and fuse: somite number 8 divides into the caudal portion of C7 and the cranial portion of T1, which means explains why.
How do cervical spinal nerves exit?
they exit above their respective vertebrae of the same number while the other spinal nerves exit below vertebrae
spinal nerve root C8 grows between C7 and T1, this explains the ratio of spinal nerves to vertebral segments
Sclerotomes form two things, and the notochord develops into something as well
Sclerotomes form neural arches around developing spinal cord and form the centrum as well
the notochord regresses and is incorporated into the intervertebral disc
Herniated intervertebral disc
the nucleus pulposeous herniates outward
Congenital scoliosis: 3 kinds
A) SEMISEGMENTED: failure of formation (there is a single wedge like vertebrae causing others to be decentered that did not form correctly)
B) BLOCK VERTEBRAE and UNSEGMENTED BAR: failure of segmentation
C) MIXED (unsegmented and semi-formed)
what is the “basic” cause of scoliosis?
abnormal formation of segmentation of somites
a treatment for scoliosis?
magnetic rods
Formation of ribs:
from where do they arise, and what region?
arise from zones of condensed mesenchyma lateral to the vertebra FROM costal processes
develop in thoracic region only
Development of Sternum:
develops from…
fuses how…
forms….
develops from cartilaginous sternal bars in ventral bony wall
fuses with one another in cranial caudal direction (top down)
forms the manubrium, body and xiphoid process
Pectus excavatum
costal cartilage overgrowth, which restricts expansion of the ribs and pushes sterum inward. largely males.
cause is truly unknown
Pectus carinatum
overgrowth of cartilage causing sternum to protrude
can be evident at birth, but mostly visible at adolescents
can occur solitary or in association with other genetic disorders
Sternal Foramen
Ossification anomaly found in 4-10% of population
CAN BE MISTAKEN FOR A BULLET HOLE!
Directly over heart
Common area for acupuncture
Appendicular skeleton development (general big picture things)
1) Hox gene expression
2) Inductive interactions between mesoderm and ectoderm
3) mechanical influences
Initiation of limb development occur what week, occurs along what axis, and is regulated by what genes?
4th wk, craniocaudal axis, Hox genes (overlapping patterns from head to tail
what axis is established first in limb development?
cranial-caudal
Cranialcaudal axis is established ____, growth is then regulated along the….axises
proximodistal, anteroposterior, dorsoventral axes
Forelimb outgrowth is initiated by
TBX5 and FGF10
Hindlimb outgrowth is initiated by
TBX4 and FGF10
TBX5, TBX4, and FGF10: which is hindlimb and which is forelimb
TBX5/FGF10 –> forelimb
TBX4/FGF10–> hindlimb
both development from lateral plate mesoderm
Holt Oram syndrome
mutation in the TBX5
important in development of both upper limbs and heart
upper limb abnormalities always present
abnormalities may be unilateral or bilateral and asymmetric
MOST PREVALENT FINDINGS ARE FUSED CARPALS or MALFORMATIONs of carpals
Holt Oram abnormalities may effect which bones of the upper limbs?
thenar, radial, ulnar bones
most prevalent findings are malformations or fusions of the carpal bones
Holt Oram:
meromelia
amelia
phocomelia
Meromelia: partial abnormality, some development
Amelia: total non-development (all limb is missing)
Phocomelia: feet an hands arise close to trunk
AER
Apical Ectodermal Ridge
thickening ectoderm on apex of limb bud
Formation of the AER
Once limb outgrowth is established, BMPs induce formation of aplical ectodermal ridge
Radical Fringe: location of expression and function
expressed in the dorsal half of limb ectoderm
restricts location of the AER to the distal top of the limbs
RF: expresses what and where
SER2 at border between cells between RF expressing cells and non-RF expressing cells
this is where AER is formed
Engrailed-1
represses expression of RF in ventral ectoderm cells
3 axes of limb development
Anterior-Post: Proximal-Distal: Dorsal-Ventral
When 3 axes are visible, what two areas control/regulate growth?
AER, ZPA, PZ
PZ
progress zone where mitosis and limb lengthening occurs
AER direct limb growth along
proximo-distal axis
AER maintains
dorsal/ventral axis
After AER is established, is expresses
FGF4 and FGF8
What do FGF4 and FGF8 do?
maintains the progress zone, which are rapidly proliferating population of mesenchyme cells adjacent to the ridge
FGF4/FGF8
maintains progress zone affects distal growth of the limb
FGF4/8 leads to
distal growth of the limb bud
ZPA
zone of polarizing activity
mesodermal cells located at base of the limb which produces retinoic acid which expresses Shh
RA leads to expression of ___ in the ZPA
Shh
ZPA directs
organization of limb bud and patterns of digits
Misexpression of RA or Shh results in
miror image reduplication of the limb structures
ZPA determines what?
Pre-axial/thumb and Posterior (postaxial)
misexpression of RA and Shh cause what?
polydactyly and duplication of AER
In Polydactyly, what is most commonly the case of the extra digit?
that it is located either medial or later
non-functional
in foot, usually lateral
dominant trait
a limb grows
proximo-distally
segmentation of the limb buds: what two zones are there
the Zone of Cell division (progress zone): region of actively dividing cells)
the Zone of Differentiation: region of cell specialization
What is the relation of Hox genes to bones?
they regulate type and shape of bones
AER secrete ____ that cells in the _____ to
FGFs, progress zone, distal structures
What happens if a cell is not within range of the AER?
it remains proximal in nature
Progress zone and FGF signaling and Thalidomide Phocomelia
FGF secreted by AER causes cells in PZ to proliferation; thalidomide disrupts this. So limb is developing but there is no growth. FGF re-specifies in PZ to become later and later distal components
Digit formation
apoptosis of webbing cells allows for digits to develop
syndactyly
failure of apoptosis, so digits are fused
Where does cell death in digit formation occur?
in the AE: creates a separate ridge for each digit
what is the most common limb abnormality?
syndactyly, most commonly between 3rd/4th finger and 2/3rd toes
simple dominant or simple recessive
Brachydactyly
short digits
uncommon, reduction in the length of the phalanges
inherited as dominant trait
short stature
Cleft hand/foot
uncommon, lobster claw
absence of one or more central digits or between fingers 2 & 4
Lateral plate mesoderm =
skeleton and vasculature
Hypaxial mesoderm =
muscles
Neural crest -
Schwann cells
Neural tube =
motor neurons/sensory axons (dermatome map)
Developing Dorsal ramus ramify through
epimeres
Developing ventral ramus ramify through
hypomeres
brachial plexus processes ramify through two regions that are split by a third region: name them
posterior process –> posterior condensation
anterior process –> anterior condensation
divides by lateral plate mesoderm
what degrees do the upper and lower limbs rotate?
90 degrees
some dorsal musculature lags behind and comes to lie on the anterior/pre-axial border (explains brachioradialis)
Sirenomelia
“mermaid syndrome” legs are fused
Congenital limb anomalies are mostly
of unknown etiology , probably multifactorial
between genetics and environment
complex interactive nature of limb development
Separation Surgery of sirenomelia (4 steps)
1) legs are fused together by skin; feet splayed in V shape
2) saline sacks progressively inserted to stretch skin
3) two operations, 3 months apart, separate the legs then use the stretched skin to cover wounds
4) last operation will rotate splayed feet forward
Achondroplasia
most prevalent form of dwarfism
mutation on FGF-R3
pathologic changes at epiphyseal plate; zones of proliferation and hypetrophy are narrow and disorganized
Achondroplasia genetics and causes
autosomal dominant
failure of proliferation
failure of column formation of epiphyseal cartilage cells
impairment causes lack of tubular bones to grow
Osteogenesis Imperfecta
also known as brittle bone disease
bone fragility that predisposes individual to deformities related to connective tissue abnormalities
blue sclera
not always evident at birth
Talipes Equinovarus
Club foot
talipes equinovarus is the most common type of club foot
sole of foot is turned medially and foot is inverted
Club foot
results from restricted movement of lower limbs in utero or abnormal position of fetus
What do the feet look like in club foot?
normal, feet are normal appearing
Feet are structurally ___ in club foot
normal
Rigid club foot
abnormal development of the ankle and foot joints during 6th/7th week
what bony deformity is particularly common in club foot?
talus
Axial skeleton is formed from
sclerotomes of the somite
appendicular skeleton is formed from
somatic lateral plate mesoderm
limb musculature develops from
hypaxial mesoderm
