Development of Limbs Flashcards
when do limb buds begin to appear
week 4
when do digits begin to appear
week 8
when does the 1st ossification occur
week 12
which limbs develop first: upper or lower
- why
upper
- blood is being pumped to the head for development; upper limb is closer to head
how does development of the limbs proceed
proximodistally
where does the muscle of the limbs originate from
paraxial mesoderm –> somite –> myotome –> hypomere –> hypaxial muscles
where do the cartilage and connective tissue of the limbs originate from
somatic layer of the lateral plate
what does the limb forming mesoderm release to stimulate the surface ectoderm to become to the apical ectodermal ridge
FGF-10
what does FGF-10 do
stimulates surface ectoderm to become the apical ectodermal ridge
what is the apical ectodermal ridge and what is it needed for
- thickening of the surface ectoderm
- needed for limb development
what does the apical ectodermal ridge release to stimulate limb mesoderm
FGF-8 and FGF-4
what does the release of FGF-8 and FGF-4 from the apical ectodermal ridge do
stimulates limb mesoderm which then proliferates and migrates to facilitate proximodistal development of the limbs
what is the most proximal region of the limb buds and what does it develop into in the upper limb
Stylopod region
- humerus, femur
what is the middle region of the limb buds and what does it develop into in the upper limb
Zeugopod
- radius/ulna and tibia/fibula
what is the most distal region of the limb buds and what does it develop into in the upper limb
Autopod
- carpals, metacarpals, digits, tarsals, metatarsals
when do the hand and foot plates develop as well as the chondrification centers
week 5
when do the digital rays of hands develop
week 6
what condenses to make bones for the digits in week 6
somatic lateral plate
at week 6 what is the entire limb skeleton made of
cartilage
when do the digital rays of the feet, rotation of the limbs, and osteogenesis of long bones begin
week 7
which develops first: hand plates or foot plates?
hand plates
when does separation of digits and apoptosis occur?
week 8
what is apoptosis due to in week 8
BMP
when do motor axons from the spinal cord enter the limb buds
week 5
Name the specific myotomes for where:
- the upper limbs develop
- the lower limbs develop
upper limbs: cervical myotomes
lower limbs: lumbar and sacral myotomes
what rotations occur in the limbs at week 7
- where do the elbows and knees now point
upper limbs rotate 90 degrees laterally
lower limbs rotate 90 degrees medially
- the elbows now point caudally and the knees point cranially
what artery does the primary axial artery become in the upper limbs
brachial artery
what artery does the primary axial artery become in the lower limbs
deep artery of the thigh
what occurs to remodel arterial supply in the limbs
angiogenesis
Club Foot (talipes Equinovarus)
- sole of foot is turned medially and inverted
- all anatomical structures are present
- 2x more frequent in males
Potential causes of Club Foot
not enough amniotic fluid so limbs cannot rotate properly
Developmental Hip Displasia
- underdevelopment of acetabulum in the hip bone (hip joint socket)
what do Hox genes regulate in limb development
- positioning of the limbs along the craniocaudal axis in proximo-distal growth
- regulate types and shapes of bones
what do things are needed for proximo-distal patterning
Apical ectodermal ridge (AER)
HOX genes
what maintains the dorsal surface in dorso-ventral patterning
Wnt7
what maintains the ventral surface in dorso-ventral patterning
BMPs
what do Wnt7 and BMP set up in patterning growth
the apical ectodermal ridge (AER)
what establishes the anterior-posterior patterning
Zone of Polarizing Activity (ZPA)
how does ZPA signal posterior elements
- what are the posterior elements
SHH and retinoic acid signaling
- digits 3-5 and ulna
loss of ZPA results in
loss of posterior elements
- ex: 4th digit, 5th digit, ulna
up-regulation of ZPA results in
additional posterior elements
- ex: polydactyly
duplication of ZPA results in
duplication of posterior elements
- ex: little fingers on both sides of the thumb
- ex: second set of toes
why can disruption of AP patterning and growth result in loss of anterior elements
posterior elements are formed prior to anterior elements
Meromelia
- when does the defect occur
results in a shrunken and deformed extremity
- defect occurs in weeks 3-5 in development
Phocomilia
shortened hands and legs
what prescribed drug used to cause meromelia
Thalidomide
brachydactyly
- how is it caused
- when
shortened digits
- FGF-8, 10, and 4 disruption in weeks 6-8
syndactyly
- how is it caused
- when
webbing of the digits
- down-regulation of BMPs needed for apoptosis in week 8
Amelia
- what is it
- when
missing both upper limbs
- weeks 3 and 4
Ectrodactyly - “Lobster Claw”
- what causes it
- when
apical ectodermal ridge was down-regulated and the digits did not form
- week 6 for hand and week 7 for feet
Arthrogryposis
congenital joint contractures
- causes unclear
