M Embryology - Limb development Flashcards
Which phase and what weeks does limb development occur?
- mid - late embryonic phase
- 4-8weeks
When are limb buds visible?
end of week 4
What are the 3 layers of the trilaminar embryonic disc?
- Ectoderm
- Mesoderm
- Endoderm
What does the ectoderm give rise to?
skin and nervous system
What does the mesoderm give rise to?
skeleton and skeletal muscle
What does the endoderm give rise to?
Epithelia lining - GI and Resp
Which 2 layers contribute to the formation of limbs?
- ectoderm
2. mesoderm
Which layer does limb bud formation start from?
mesoderm
Which layer is the limb bud core made up of and which part of this layer is it derived from?
mesoderm
derived from - lateral plate mesoderm
What is the core of the limb bud covered by and what does this eventually form?
ectoderm
skin/epidermis
Why does the mesoderm core condense and what does it differentiate into?
to form bone and connective tissues
mesenchyme
Which layer of the mesoderm is skeletal muscle derived from?
paraxial mesoderm
What are somites?
blocks or subdivisions of paraxial mesoderm
Why are somites important?
formation of skeletal muscles
surrounding the vertical column and neural tube
What are the 2 parts of the dermomyotome?
- dermatome - skin
2. myotome - skeletal muscle
Where is the dermomyotome derived from?
somites
What 2 parts does the myotome split into?
- dorsal part = EPIMERE
2. ventral part = HYPOMERE
What does the epimere form?
the muscles of the dorsum/back
What does the hypomere form?
the muscles of the thorax and abdomen
Where are the upper limb muscles derived from and what level?
hypomere
level of C5-C8
Where are the lower limb muscles derived from and what level?
hypomere
level L3-L5
What 2 parts does the hypomere divide into?
- posterior condensation
2. anterior condensation
What muscles do the posterior condensation include?
UPPER LIMB
extensors and supinators
LOWER LIMB
extensors and abductors
What muscles does the anterior condensation include?
UPPER LIMB
flexors and pronators
LOWER LIMB
Flexors and adductors
What spinal nerves are associated with the epimere muscles?
dorsal rami
What spinal nerves are associated with the hypomere muscles?
ventral rami
What are the limb buds initially innervated by?
branches of the ventral primary rami of the spinal nerves
What is the upper limb innervated by?
Brachial plexus
C5-T1
What is the lower limb innervated by?
lumbosacral plexus
L4-S3
Why does the anterior and posterior compartment of limbs have different nerve supplies?
As the spinal nerves of the limb bud migrates and splits into anterior and posterior branches.
Why is limb rotation necessary?
makes sure limbs don’t meet each other
When does limb rotation occur (which weeks)?
between 6 and 8 weeks
How do the upper limbs rotate and why do they rotate in this way?
90 degrees laterally
flexors lie anteriorly
How od the lower limbs rotate and why do they rotate in this way?
90 degrees medially
flexors lie posteriorly
What effect does limb rotation have on the dermatomes?
causes sensory dermatomes to spiral round limbs
What are dermatomes and what injury does it allow to be tested?
band of skin supplied by one pair of spinal nerves
spinal cord injuries - test levels of the spinal cord
NOTE
learn dermatomes
What 3 axes does the limb develop along?
- proximodistal
- cranocaudal
- dorsoventral
Where does the proximodistal axis run and what is it’s role?
RUN
shoulder to hip to hand/foot
ROLE
lengthening limb away from the body
Where does the craniocaudal axis make sure and what is it’s role?
MAKES SURE
thumb is most cranial digit and the little finger most caudal
ROLE
makes sure digits (fingers and toes) end up in correct position
What does the dorsoventral axis do?
Makes sure the palm of the hand and the sole of the foot are ventral = SOFT
Makes sure the knuckle side of hand/foot is dorsal = HARD
What is formed in the proximodistal outgrowth?
apical ectodermal ridge
What does the lateral plate mesoderm secrete?
Fibroblast growth factor - Fgf 10
What does Fgf-10 induce and what does this form?
- thickening of the overlying ectoderm along the tip of the limb bud
this forms the Apical ectodermal ridge - AER
What does the apical ectodermal ridge do?
drives growth of limb bud
What does the apical ectodermal ridge express?
Fibroblastic growth factors
- Fgf 4
- Fgf 8
What does Fgf-4 and Fgf-8 cause?
- rapid proliferation of the mesenchymal cells underlying the apical ectodermal ridge
- forms the PROGRESS ZONE
What does the progress zone do?
maintains proximodistal outgrowth of limb
What happens if you remove the apical ectodermal ridge?
the rest of the limb with halt growth
What controls dorsoventral patterning, what does it do and what is it expressed by?
Wnt7
controls morphology of palm and nails
by dorsal ectoderm
What inhibits Wnt7 and where is it derived from?
Engrailed-1
ventral ectoderm
What happens if you remove Wnt7?
palmar structures form on back of the hand
What is craniocaudal patterning controlled by?
Zone of polarising activity (ZPA)
- small region of mesenchyme in the caudal limb part
- where sonic the hedgehog (SHH) is expressed
What does sonic the hedgehog (SHH) do ?
HIGH CONC
induces formation of caudal structures - little finger
LOW CONC
induces formation of cranial structures - thumb
Where does Sonic the hedgehog diffuse from and in which direction?
From - ZPA
Cranial direction
What does transplantation of ZPA induce?
mirror image polydactyly
In which week does digit formation occur?
week 6
How are fingers and toes formed?
Apoptosis in apical ectodermal ridge
What types of limb malformations are there? (7)
- amelia
- meromelia
- phocomelia
- phenomelia
- syndactyly
- polydactly
- ectrodactyly
Amelia - what is it and what is it due to?
complete absence of a limb
lack of Fgf signalling
Meromelia - what is it and what is it due to?
partial absence of a limb
later/partial loss of Fgf signalling or AER removed
less severe
Phocomelia - what is it and what is it due to?
digits develop prematurely and proximal elements of limbs are absent
- flipper limb
- shortened limbs
lack of proximodistal growth - Thalidomide
What is thalidomide used to treat nowadays?
Leprosy and HIV
Syndactyly - what it is and what is it caused by?
fused digits
failure of apoptosis
Polydactyly - what is it and what is caused by?
extra digits
inappropriate SHH expression
Ectrodactyly - what is it and what is it caused by?
split hand/foot - lobster claw deformity
failure of middle of the AER formation hence defect in proximodistal outgrowth
