Limb Development Flashcards
What week does limb development start? Does upper extremity or lower extremity develop first?
During week 4, upper extremity starts forming first
What week do the digits start to form?
week 8
What three things are involved in developing the limbs (cell wise)? (3)
Muscle from somite mesoderm (paraxial) (hypomere)
Cartilage from lateral plate somatic mesoderm
Connective tissue from lateral plate somatic mesoderm (mesenchymal)
What consists of limb forming mesoderm?
Paraxial and lateral plate mesoderm
What does FGF10 do and where does it come from?
From the limb-forming mesoderm, will stimulate surface ectoderm to become the apical ectodermal ridge (thickening of surface ectoderm needed for limb development)
What will the apical ectodermal ridge release to stimulate limb mesoderm?
FGF 8 and 4
Once the reciprical signaling occurs between the limb forming mesoderm and the apical ectoderm ridge (FGF 10,4 & 8), what occurs?
The limb cells will proliferate and will grow from proximal to distal
What is unique of the limb-bud mesoderm?
the different areas of mesoderm are preprogrammed to become different regions of bone
What are the three regions of the limb bud before growth and what do they form? (proximal, middle, distal (grow in that order) )
Stylopod, proximal: humerus and femur
Zeugopod, middle: radius/ulna, tibia/fubla
Autopod, distal region: carpals, metacarpals and digits, as well as tarsal, metatarsal and digits in foot
What forms during week 5?
hand and foot plates, hand before foot (little paddles)
chondrification centers appear
What forms/happens during week 6?
formation of digital rays of hands (somatic layer of lateral plate) bones/ beginning of digits
entire limb skeleton is cartilaginous
What forms/ happens during week 7?
somatic mesoderm layer of lateral plate will condense to form bones/ digital rays of feet (beginning of digits)
osteogenesis of long bones begin, rotation of limbs
What forms during week 8?
separate digits are formed due to apoptosis by BMP family (need BMP for cells to undergo apoptosis to separate fingers so we do not get webbed/fused fingers)
Where do the upper limb bud and lower limb bud form in mytomes?
Upper arm: cervical region
Lower leg: lumbar/sacral region
What is the difference in rotation of lower and upper limb by the end of week 7?
The upper limb rotates laterally 90 degrees
the lower limb rotates medially 90 degrees
hence why there is a huge difference
For blood supply of the limbs, intersegmental arteries come from the dorsal aorta. What do the intersegmental arteries become in the upper and lower limb?
The primary axial artery
What does the primary axial artery give rise to in the upper limb?
Common interosseous and brachial artery
What does the primary axial artery give rise to in the lower limb?
deep artery of the thigh and the posterior tibial artery
What occurs in club foot (every 1 in 1000 births)?
The foot is turned in medially and inverted, otherwise normal
How is club foot generally fixed?
Casting, taping and in serious cases surgery
What is developmental hip dysplasia (in more females)?
the under development of the acetabulum (hip socket) of the hip bone/ head of femur. a lead heart shaped cover is placed over the ovaries to do xray
What is needed for proximo-distal growth and patterning?
the apical ectodermal ridge (from ectoderm) and the signaling of FGF 10 from limb-forming mesoderm and FGF 4 and 8 from the apical ectodermal ridge & HOX genes
What is needed for dorso (extensors) -ventral (flexors) patterning?
The ventral surface is maintained by the BMPS and the dorsal surface is maintained by the Wnt7, this is set up by the apical ectodermal ridge (AER)
What is needed for anterior posterior patterning of the limb?
Zone of polarizing activity (ZPA) on the posterior side of the limb (what would be the pinky finger area)
What does the zone of polarizing activity (ZPA) release?
SHH and retinoic acid signals the posterior elements of digits 3-5
What occurs when there is a loss, upregulation, or duplication of ZPA?
Loss: lose post. aspect/ digit
Upreg: additional digits/posterior aspects
Duplication: mirror image of little fingers on either side of thumb
What is formed first, anterior or posterior elements
Posterior elements (ulna and little finger) are formed first, anterior elements (radius and thumb) are formed after
A child has polydactyly (extra finger), what week did this abnormality occur and how?
Week 6 when the digital rays form, and it is caused by an upregulation of ZPA
A child has polydactyly (extra three alongside thumb), what week did this abnormality occur and how?
Week 7 when foot digital rays form, caused by a duplicate ZPA zone, due to 3 extra/mirror digits
A child has brachydactyly (short fingers), what week did this abnormality occur and how?
Due to proximal-distal growth abnormalities at apical ectodermal ridge, lack of FGF 10,4,8 (AUTOPOD)
week 6-8
A child has syndactyl (fusion of toe), what week did this abnormality occur and how?
Week 8, down regulation of BMPs during week 8 needed for apoptosis to get separation of digits
A childer has meromelia-phocomelia (short limbs commonly caused by thalidomide in 50s), what week did this abnormaily occur and how?
Weeks 3-4-5, apical ectodermal ridge issues, FGF 4&8 or lack of vasculature
Amelia is where no upper limbs form, when does this occur?
Weeks 3/4
Split hand/foot, also know as lobster claw or ectrodactyly (get first and 5th digit only), what week does it occur for hands and feet, and how?
**** IMPORTANT Center of apical ectodermal ridge was downregulated, and the middle fingers were not formed at all. Hands during week 6, feet during week 7
What is arthrogryposis and what are the possible causes?
Congenital joint contractures
Due to: neurological defects, muscular abnormalities, joint and connective tissue problems and fetal crowding(no movement)
