Limb Development Flashcards
What are the limbs derived from?
Somatic Lateral Plate Mesoderm
Where do the upper limb buds develop?
Opposite the lower 5 cervical and upper 1 or 2 thoracic levels
Where do the lower limb buds develop?
Opposite the lower 4 lumbar and upper 2 sacral levels
Where do the limb muscles come from?
Primarily from Myotome Migration
-cells from somites migrate into limb buds to develop into muscle
Describe innervation of the limbs
Innervated by branches from the nerve plexus based on limb position
Where do nerves supplying the limb skeletal muscle fibers arise from?
Motor neurons in the ventral horn of spinal segments
What allows for longitudinal growth of long bones during childhood?
Growth plate, or epiphysis
-made of cartilage
Where is the epiphysis located?
between the metaphysis and the epiphysis on all long bone
What are the 4 zones of the epiphysis?
germinal, proliferative, hypertrophic and provisional calcification
*first two provide cellular proliferation while the latter two zones are where matrix production, cellular hypertrophy, apoptosis and matrix calcification occur
When does ossification of long bones begin?
3rd month of development
When do most primary ossification centers appear in the diaphysis of bone?
4th month
When do secondary ossification centers appear in the epiphyses?
Birth - 5 years
When do bones of the UE and scapulae become completely ossified?
17 to 20 years
When do bones of the LE and coccyx become completely ossified?
18-23 years
When do the sternum, clavicle and vertebrae become completely ossified?
23-25 years
When are all bones completely ossified?
By 25 years
What stimulates the elongation of the long bones?
somatotropin
When does bone elongation cease?
When elevated levels of testosterone or estrogen cause the fusion of the epiphyseal and shaft ossification centers and the loss of the epiphyseal plate
How many ossification sites are found in the vertebrae at birth?
3
How many ossification sites are found in the vertebrae at age 16?
8
How many bones are in the appendicular skeleton?
126
How many bones are in the axial skeleton?
80
Approximately how many skeletal muscles does a typical human have?
640 skeletal muscles
320 pairs of muscles
2 largest muscles
gluteus maximus and vastus lateralis
What is the smallest skeletal muscle?
the stapedius of the middle ear
3 types of muscle
1) Skeletal
2) Smooth
3) Cardiac
Describe back muscles
These muscles are actually muscles of the upper limb that have migrated to cover some of the true back muscles.
Back muscles re innervated by what?
Where do they originate?
ventral primary rami and have their origin in hypomeres associated with limb segments.
On average how many neurons does the average human brain contain?
86 billion
When do limb buds begin to appear?
Around the 28th day of development
Do the upper or lower limb buds appear first?
The upper limb bud appears before the lower limb bud by one or two days
When do upper limbs begin to develop?
At 4 weeks
When do the cartilage models for the limb buds begin to form?
At 6 weeks
When do primary centers of ossification appear by in the limbs?
8-12 weeks (in diaphysis), or sooner (as early as 6 weeks)
When does endochondral ossification begin?
during the eighth week or thereafter, but as early at the 6th
When do secondary centers of ossification generally appear?
After birth
What is a limb bud?
an accumulation of mesoderm from the somatic layer of lateral plate mesoderm with contributions from the adjacent somites
What is the AER
Apical Ectodermal Ridge
-the mesoderm induces the overlying ectoderm and forms this
What happens if the AER is removed?
the limb stops development at the stage it was removed
When is limb development first evident?
On about day 26 when mesenchymal cells migrate out of the somatic lateral plate mesoderm and accumulate under the epidermis as a cluster of pluripotent blastema cells
What are the 3 limbs axes?
(1) Anteroposterior
(2) Dorsoventral
(3) Proxiodistal
The limbs have a _______to ______ developmental pattern.
Proximal
Distal
What else does the AER influence?
the underlying limb mesoderm (mesenchyme)
Which protein is required for limb bud formation?
Fibroblast growth factor 10 (FGF10)
What is the ZPA?
The Zone of Polarizing Activity
It is a cluster of cells at the posterior border of the limb near the cell wall that regulates the patterning of the anteoposterior axis of the limb
What do ZPA secrete?
Sonic hedgehog (Shh)
What is Shh responsible for?
Required for patterning the posterior digits of the vertebrate limb.
PATTERN FORMATION
The Sonic hedgehog gene is the key inductive signal in patterning what 3 things?
1) The ventral neural tube
2) The anterior-posterior limb axis
3) The ventral somites
Mutations of the Shh gene result in what?
VACTERL syndrome and preaxial polydactyly
What are HOX genes?
Genes responsible for the fine-tuning of positional information and precise control of limb patterning
What is the proximal-distal axis of limb development regulated by?
Fibroblast Growth Factors (FGF)
What is the anterior-posterior axis of limb development regulated by?
Sonic Hedgehog (Shh)
What is the Dorsal-Ventral axis of limb development regulated by?
WNT-7a (which is produced by Dorsal Ectoderm)
What does correct morphogenesis of our limbs depend on?
The appropriate spatial and temporal balance between cell death and cell proliferation.
What does the position of future joints is first delimited by?
areas of higher cell density called interzones
What is cavitation?
Skeletal joint cavity development
When does joint generation begin?
4 to 7 weeks of gestation
Apoptosis vs. Necrosis
Apoptosis is genetically programmed cell death
Necrosis is premature cell and tissue damage due to external factors
3 Types of Joints
1) Synovial (freely movable)
2) Cartilaginous (partially movable)
3) Fibrous (immovable)
2 types of cartilage connecting cartilaginous joints
fibrocartilage or hyaline cartilage
2 types of cartilaginous joints
1) symphyses (pubic symphysis)
2) synchondroses (growth plates)
Where are fibrous joints found?
cranial vault and teeth
3 Types of Fibrous Joints
1) Sutures (skull)
2) Syndesmoses (fibula and tibia ligament)
3) Gomphoses (teeth)
How does early myotome develop?
Through the division of the epaxial and hypaxial myotome regions.
How is the epaxial myotome formed?
by myoblasts derived from the dorsomedial lip (DM) of the dermomyotome
How is the hypaxial myotome formed?
by myoblasts derived from the ventrolateral lip (VL) of the dermomyotome
What does the hypaxial dermomyotome give rise to?
body wall muscles and intercostal muscles
What does the epaxial dermomyotome give rise to?
muscles of the deep back
What do muscle growth and regeneration events in the adult body depend upon?
the proliferation and differentiation of muscle stem cells, called satellite cells
Where are satellite cells located?
under the basal lamina of muscle fibers
How does a muscle heal itself?
Upon injury satellite cells are activated, migrate to the injured area, proliferate, and fuse with each other to replace degenerated muscle fibers.
Where do myotomes C5-T1 migrate to?
Into the upper limb
Where do myotomes C5-C6 migrate to?
proximal parts of the upper limb (thumb side)
Where do myotomes C8-T1 migrate to?
more distal parts of the limb segments (pinky side)
Myotome/motor innervation is via what?
ventral horn (basal plate) neurons
Where does limb mesoderm come from?
the somite and lateral plate mesoderm
What does the lateral plate mesoderm contribute to? (3 things)
the skeleton, blood vessels & connective tissue
What does the somite mesoderm contribute to?
the Musculature
Nerve cells & Neural crest cells
What do neural crest cells give rise to? (3 things)
sensory nerves, Schwann cells, pigment cells
Describe Myotome Growth Initially and then Later On
Growth initially occurs by a contribution of myogenic progenitor cells from the medial border of the dermomyotome.
Later by progenitors from all four borders of the dermomyotome, with the medial and the lateral borders of the somite generate the epaxial and hypaxial muscles.
Depending on the somite level within the body, myotome cells will then give rise to limb and trunk muscles.
What specifies motorneuron projections in the limb?
Axon guidance signals
How can you tell where a muscle originated?
By its innervation
Which nerves supply the extensors and which supply the flexors?
Radial and axillary nerves supply extensors.
Medial and ulnar nerves supply flexors.
Describe the rotation of the limbs during development
the upper limb rotates 90 degrees laterally (external)
the lower limb rotates 90 degrees medially (internal)
**in other words the anterior aspects of the upper limb are homologous to the posterior aspects of the lower limb.
A myotome is the sum of _____ supplied by a single spinal ____ or ____ nerve.
skeletal muscle
spinal
cranial
What is Amelia?
absence of limbs
What is meromelia?
abesnece of part of a limb
What is micromelia?
limb present but all parts shortened
What is syndactyl?
Webbing of fingers/toes resulting from failure of interdigital cleft to form
3 Types of Cartilage and Examples of Each
- Hyaline cartilage (e.g., in joints)
- Fibrocartilage (e.g., in intervertebral discs)
- Elastic cartilage (e.g., in auricles of the external ears)
Mesenchymal cells from the sclerotomes are found in what three main areas?
1) around the notochord
2) surrounding the neural tube
3) in the body wall
