T14- Limb development Flashcards
Differentiation of Limb buds
Where is FGF highly concentrated
at the distal aspect of the limb
Upper limb buds form ___________ to _________ vertebral segments
adjacent; cervical
What does the mesenchymal core of the limb bud eventually become
the bones and muscles
Signaling in limb development
FGF-10 ___________ FGF-8 which is in the overlying _________. A _______ feedback loop ensues
stimulates; ectoderm; positive
Development of limb buds
When are notches formed in the upper limb
about day 46
What do limb buds consist of initially?
a mesenchymal core and a layer of surface ectoderm
Development of limb buds
What is the second step
Condensation of mesenchymal core tissue in plates to form digital rays that each have an AER tip
Cell contribution to limb development
Neural Tube cells
contribute to formation of motor axons
Formation of limb muscle
Where do myogenic precursor cells first cluster
at the base of the limb buds
Development of limb buds
When does digital ray formation in the hands happen
In the 6th week (day 41)
Signaling in limb development
What does Hox-4/5 stimulate?
Tbx-5
Elongation and differentiation along the craniocaudal axis
What does the ZPA express
Sonic hedgehog
Limb development
What happens in carnigie stage 19
The limbs extend ventrally (end of week 7)
Formation of limb skeleton
What is the diaphysis of the long bone
the shaft of the long bone
Formation of limb skeleton
What happens by the end of week 6 (day 42)
entire limb skeleton is a hyaline cartilage bone model
Development of limb buds
When does digital ray formation in the feet happen?
In the 7th week (day 46)
Cell contribution to limb development
Somites
contribute to formation of myoblasts and endothelial cell precursors
What is complex (osteus) syndactyly
less common than cutaneous syndactyly and is a result of failure of the digital rays to separate
Elongation and differentiation along the craniocaudal axis
What does the SHH that the ZPA expresses ensure
SHH ensures that the digits appear in the correct order (thumb on cranial side and pinky on caudal side)
Positional changes of developing limbs
Initial state of limbs
Limbs initially extend ventrally; palms/soles face each other; elbows/knees point laterally
Elongation of limb buds
What happens to the apex of each limb bud in response to the FGF positive feed back loop
apical ectodermal ridge (AER) forms
Formation of limb muscle
How do myogenic precursor cells differentiate
they migrate into limb buds, undergo epitheliomesenchymal transformation and differentiate into myoblasts
Development of limb buds
When are separate digits formed in the lower limb
about day 55
Formation of limb muscle
How are extensors and flexors formed
myoblasts aggregate on either side of long bone
Limb development
What happens in carnigie stage 13
Lower limb buds appear (between week 4 and 5)
Limb development
What happens in caringie stage 15
The hand plates form and the digital rays are visible (end of week 5)
Elongation of limb buds
Where is the AER located
along the border between dorsal and ventral limb ectoderm
Formation of limb skeleton
When does the mesenchyme turn into cartilage?
in the 5th week
Formation of limb skeleton
What does the the chondrification center do
it turns the mesenchyme into cartilage
Positional changes of developing limbs
Rotation of upper limbs
Upper limbs rotate externally 90 degrees resulting in:
- elbows pointing caudally
- flexor muscles found along anterior limb surface
- extensor muscles found along posterior limb surface
Differentiation of Limb buds
Where is Retinoic acid highly concentrated
at the proximal aspect of the limb
Limb development
What happens in carnigie stage 21
Hands and feet approach each other; fingers and toes are free and longer; toes are distinct but webbed
Differentiation of Limb buds
Where does retinoic acid come from
the somites
Formation of limb skeleton
Where are secondary ossifcation centers located at birth
Distal femur and proximal tibia
Elongation of limb buds
How does AER promote limb bud elongation?
it induces the adjacent mesenchyme to remain undifferentiated and to rapidly proliferate; occurs in the progress zone
Differentiation of Limb buds
Where is Retinoic acid minimally concentrated
at the distal aspect of the limb
Formation of limb skeleton
What is the epiphysis of the long
the ends of the long bone
Formation of limb muscle
What are skeletal muscles of limbs formed from
myogenic precursor cells (including migrated somite cells)
Lower limb buds form adjacent to ___________ and ___________ vertebral segments
caudal lumbar; cranial sacral
What determines the craniocaudal location of limb buds
Hox genes
Development of limb buds
When are separate digits formed in the upper limb
about day 52
What are the three axes of limb development
Proximodistal , Craniocaudal, Dorsoventral
Differentiation of Limb buds
What does retinoic acid contribute to?
limb differentiation
Development of limb buds
What is the third step?
The loose mesenchyme that makes up the webbed intervals of the digital rays undergoes apoptosis, which forms notches then separate digits
Signaling in limb development
What does HoxC -8,-9,-10 stimulate and repress
it stimulates Tbx-4 but represses Tbx-5
Formation of limb skeleton
What is the epiphyseal cartialage plate
cartilage plate between the shaft and each end
Positional changes of developing limbs
Rotation of lower limbs
Lower limbs rotate internally 90 degrees resulting in:
- knees pointing cranially
- flexor muscles being found along the posterior limb surface
- extensor muscles being found along the anterior limb surface
Development of limb buds
What is the first step
The distal portion of the limb buds flatten around the AER forming the hand+foot plate
Differentiation of Limb buds
Order of differentiation
stylopodium -> zeugopodium -> autopodium
What does the surface ectoderm eventually become
the skin
What is cutaneous syndactyly
failure of digits to separate due to failure of cellular apoptosis
What is polydactyly
More than 5 digids on a limb
Elongation and differentiation along the dorsoventral axis
Which protien is expressed by the dorsal non AER ectoderm
WNT-7a
Signaling in limb development
Where are Hox genes expressed
in lateral plate mesoderm
Cell contribution to limb development
Lateral plate mesoderm
contibutes to formation of the skeleton, CT, and some BV’s
Limb development
What happens in caringie stage 12
the upper limb buds appear (week 4)
Cell contribution to limb development
Neural crest cells
contribute to formation of pigment cells, sensory axons, and schwaan cells
Elongation of limb buds
Where is the zone of polarizing activity found (ZPA)
at the proximal, caudal border of the limb
Formation of limb skeleton
When does ossification of limb long bones begin
at the end of the embryonic period (day 56)
Limb development
What happens in carnigie stage 16
The foot plates are formed (week 6)
Limb development
What happens in carnigie stage 17
Digital rays are clearly visible in hand plates (end of week 6)
Elongation and differentiation along the dorsoventral axis
What does LMX-1 expression determine
that the extensors are located dorsally
Elongation and differentiation along the dorsoventral axis
What does WNT-7a induce?
expression of LMX-1
Elongation and differentiation along the dorsoventral axis
Which protien is expressed by the ventral non-AER ectoderm
Engrailed-1 (En-1)
Signaling in limb development
What do Tbx-5 and Tbx-4 stimulate
Fibroblast growth factors (FGF’s)
Development of limb buds
When are notches formed in the lower limb
about day 49
Differentiation of Limb buds
Where is FGF minimally concentrated?
at the proximal aspect of the limb
Elongation of limb buds
What does AER promote
Limb bud elongation
Elongation of limb buds
What happens as the limb buds grow?
proximal cells move further away from the progress zone and because of this, they are under less influence by the AER so they will begin to differentiate
When do upper and lower limb buds form
towards the end of the 4th week
Elongation and differentiation along the craniocaudal axis
What happens to the ZPA
As the limbs grow along the proximodistal axis, the ZPA moves distally so that it remains in close contact with the caudal ectoderm of the AER
Limb development
What happens in carnigie stage 22
toes are free and longer
Formation of limb skeleton
When are primary ossification centers found in all long bones
by week 12
Limb development
What happens in carnigie stage 18
digital rays are clearly visible in the foot plates and the elbow reigon is visible; there are notches between digital rays in the hand (week 7)
Signaling in limb development
Where is HoxC-8,-9,-10 expressed?
Near the upper location where the lower limbs are formed
Limb development
What happens in carnigie stage 20
The upper limbs are longer and are bent at the elbows; fingers are distinct but webbed; notches between digital rays in the feet (end of week 7, beginning of week 8)
Signaling in limb development
Where is Hox-4/5 expressed
near the location where the upper limbs are formed
Elongation and differentiation along the dorsoventral axis
What does Engrailed-1 expression deterimine
that the flexors are located ventrally
