Limb Development Flashcards
When do upper and lower limb appear compared to each other?
- Paired upper and lower limb buds appear as small elevation of ventrolateral body wall by the 4th week of development.
- Upper limb buds are visible by day 26 or 27, whereas lower limb buds appear 1 or 2 days later
- Upper limb buds develop opposite the caudal cervical segment, whereas the lower limb bud develop opposite the lumbar and upper sacral segment
What does a limb bud consist of?
- A mesenchymal core:
- derived from somatic layer of lateral plate mesoderm
-covered by ectoderm
How does limb development initiate?
Activation of mesenchymal cells in the lateral mesoderm starts off the process of limb development (elongation)
Contrast the divisions of mesoderm and what they develop into
Paraxial mesoderm- divides into 42-44 pairs of somites
Intermediate mesoderm- urogenital system
Lateral plate mesoderm:
- subdivision of the intraembryonic (secondary) mesoderm
- forms the connective tissue of the limbs
Somites give rise to:
Somites gives rise to:
-sclerotome= vertebrae & ribs
- myotome= muscle
- dermatome= connective tissue-dermis
What initiates the development of the limb?
The homeobox (HOX) gene initiates the process
- Activation of mesenchyme induces formation of an Apical ectidermal ridge (AER)
- Mesenchyme condenses and gives rise to the skeleton & connective tissue
What is the function of the Apical ectodermal ridge(AER)?
Apical ectodermal ridge(AER)
- Ectodermal thinking at the apex of each limb bud
- Inductive influence on limb mesenchyme
- Stimulate proliferation of mesenchyme
- Progress zone
- Stimulate proliferation of mesenchyme
- Growth and development of the limbs
- Proximaldistal axis
Interaction between the AER and mesenchyme is essential for limb development
What is the signal center and molecular signal for the proximodistal axis?
Signaling center: apical ectodermal ridge(AER)
Molecular signal: fibroblast growth factors (FGF-2, -4,-8)
What are the signaling center and molecular signals of the anteroposterior axis?
Signaling center: zone of polarizing activity(ZPA)
Molecular signal: sonic hedgehog (shh)
What are the signaling centers and molecular signal of the dorsi ventral axis?
Signaling center- dorsal ectoderm
Molecular signal- Wnt-7a(dorsal)
Signaling center- Ventral ectoderm
Molecular signal- En- 1 (ventral)
Summarize week 4 of limb development
28 days
-Limb buds appear as small elevations of the ventrolateral body wall
- Upper limb buds appear by 26th-27th day
- Opposite C5-T1 spinal segments
Lower limb buds appear about 2 days later
-opposite L4-S3 spinal segments
Summarize week 5 of limb development
32 days of hand and foot plates
What occurs during week 6 and week 7 of limb development?
42 days
Week 6
-Mesenchymal tissue in the hand plates condense to form digital ray(finger buds), outlines the pattern of the digits
Week 7
-Mesenchymal tissue in the foot plates condense to form digital ray( toe buds), outlines the pattern of the digits
- Tissue between digital rays undergoes apoptosis (programmed cell death)
- Forming notches between the digit rays
What are the events occurring in the 5 the week of limb development?
56 days
-fingers and toes are distinct and separated
Summarize limb development, week by week
Week 4
-limb buds appear
Week 5
-hand & foot plates formed
Week 6
- digital rays appear
- tissue between digital rays undergoes apoptosis
- form notches
Week 7
- Upper limbs bend at elbow
- Fingers are short and webbed
Week 8
-Digits are distinct and separated
What are the positional changes of developing limbs?
A. 48 days
- limbs extend ventrally
- Hand plates & foot plates face each other
B. 51 days
- Upper limbs bent at elbows
- Hands curved over the thorax
C. 54 Days
-Soles of feet medially
D. 56 days
- Elbows point caudally
- knees point cranially
How are limbs rotated?
Upper limb rotates 90 degrees laterally
- flexors-anteriorly
- extensors-posterior
Lower limb rotates 90 degrees medially
- extensors anterior
- flexors- posterior
Summarize development of cartilaginous bones
- chondrofication centers form during 5th week
- By 6th week, the entire limb skeleton is cartilaginous
- Osteogenesis of the long bones begins in the 7th week
- Primary ossification centers
-Ossification of the carpal and tarsal bones begins in the first year after birth
How are bones and limb girdles formed?
Bones of the limbs & limb girdles are formed by endochondrial ossification (except for the clavicle)
-mesenchymal cells give rise to a cartilaginous model which subsequently ossifies
Summarize ossification of the appendicular skeleton
- Diaphysis
- Formed by primary center of ossification
- Appear by 7th - 8th week
- Formed by primary center of ossification
- Epiphysis
- Formed by secondary centers of ossification
- Appear during first 4 years
- Formed by secondary centers of ossification
- Epiphyseal plate
- Growth plate between diaphysis and epiphysis
- Adds length to the bone
- Persist until growth period is over
Where are the primary centers for ossification?
Primary centers of ossification present in most long bones of appendicular skeleton
Some areas remain cartilaginous
-epiphyses of long bones
-carpus and tarsus
What are myotomes?
- Musculature of limbs develops from hypaxial divisions of myotomes
- Myogenic precursor cells migrate into the limb bud and differentiate into myoblasts
- As long bones form, myoblasts aggregate and form a muscle mass I; each limb bud
- This muscle mass separate into flexor and extensor compartments
When are dermatomes formed ?
Motor axons arise from the spinal cord and enter limb bud during the 5th week
Sensory axons enter limb buds after the motor axons
-use them for guidance
Neural crest cells are…
- Precursors of Schwann cells
- Surround motor and sensory nerve fibers in the limbs
- Form the neurolemma and myelin sheaths
What is a dermatome?
An area of skin supplied by a single spinal nerve and its spinal ganglion
Spinal nerves are distributed in the segmental bands & their orderly sequence of distribution can be recognized even after growth of the limbs
How are limb arteries developed?
Limb buds supplied by branches of the intersegmental arteries
- Arise from dorsal aorta
- Form fine capillary network throughout mesenchyme
Primordial vascular pattern
-Primary axial artery & it’s branches
What is the frequency of syndactyly?
1:2200 births
What are the types of syndactyly?
Cutaneous syndactyly(most common limb defect) -webbing of the digits-failure of webs to degenerate between 2 or more digits
Osseous syndactyly
-fusion of the bones- failure of development of notches between the digital rays
What is polydactyly?
Supernumerary digits
- disruption of anterior posterior pattern
- inherited as a dominant trait
What is club foot(congenital talipes)?
- Talipes equinovarus (is the most common type)
- Twice more frequently in males as in females
- Sole of foot is turned medially and foot is inverted
- Multifactorial pattern of inheritance
What is Amelia?
- Complete absence of limbs
- Suppression of limb bud development in the 4th week
What is meromelia?
Partial absence of limbs
-disturbance of limb development during 5th week
What are amelia and meromelia defects caused by?
- genetic factors
- mutant genes
- environmental factors
- vascular disruption and ischemia
What are cleft hand and cleft foot (ectrodactyly)?
- absence of one or more central digits
- Failure of development of one or more digital rays
-Remaining digits are partially or completely fused
- Rare anomaly
- Lobster claw deformities
What is amniotic band syndrome?
Tears in the amnion result in amniotic bands
- May encircle fetal limbs & digits
- Ring constrictions
- Amputations
What is the cause of amniotic band syndrome?
Cause unknown
-May be due to infection
What is the frequency of amniotic band syndrome?
About 1:1200 live births
What is the frequency of vecterl syndrome?
Occurs in 1 in 10,000 to 40,000 births.
What is the cause of vecterl syndrome?
Caused by the interaction of multiple genetic and environmental factors
What are the characteristics of vecterl syndrome?
- vertebral defects
- anal atresia
- cardiac defects
- Tracheo-oesophageal fistulga
- Renal anomalies
- Limb anomalies
People diagnosed with VECTERL association typically have at least three of these characteristics
