Limb Development Flashcards
At what week in development do limb buds form?
Week 4
At what week in development are the digits fully formed?
Week 8
Limbs are formed from muscle, cartilage, and connective tissue. What are the germ layers each of these are derived from?
Muscles = Somite mesoderm (Myotome – Hypomere)
Cartilage (including bone) = Somatic layer of lateral plate mesoderm
CT = Somatic layer of lateral plate mesoderm
***Remember somites come from Paraxial Mesoderm!
This structure is a mix of Somites (hypomere) and somatic layer of the lateral plate mesoderm. It produces FGF-10.
Limb-forming mesoderm
What signal does Limb-forming Mesoderm give off?
FGF-10
When Limb-forming Mesoderm signals FGF-10, what is formed?
Apical Ectodermal Ridge (AER)
***Made from Surface Ectoderm and is what gives us limb-bud ectoderm
T/F. As the AER grows out distally, the limb-bud mesoderm (beneath) gives off different signals. These signals turn on genetic programs that make certain cells already know what bones they’re going to become.
True
Limbs develop proximodistally. First the ________ is formed, which creates the Humerus and Femur.
Stylopod
Limbs develop proximodistally. Second the ________ is formed, which creates the Radius/Ulna and Tibia/Fibula.
Zeugopod
***Distal to Stylopod
Limbs develop proximodistally. Third the ________ is formed, which creates the Carpels, Metacarpals, Digits, and Tarsals, Metatarsals, and Digits.
Autopod
***Distal to Zeugopod
At what week in development do the hand and foot plates form and the chondrification centers appear?
Week 5
At what week in development is the entire limb skeleton cartilaginous and the digital rays of the hands form?
Week 6
At what week in development does the digital rays of the feet form, rotation of limbs, and osteogenesis of long bones begin?
Week 7
During weeks 6 and 7 the digital rays of hands and feet form because…
Mesenchymal cells condense to form digits
***Embryologic stem cells – mesoderm
During week 8, individual digits are formed due to apoptosis which kills the skin cells that are webbed between fingers and toes. This apoptosis is controlled by what signal?
BMPs
Limb musculature is derived from dorsolateral cells of the ________.
Somites
Motor axons from spinal cord enter the limb buds during the ______ week (neuroectoderm).
5th
Sensory axons follow the motor axons and use them for guidance. Sensory axons are from which germ layer?
Neural Crest
Neural crest cells become what type of cell for myelination (in PNS)?
Schwann Cells
At week 7 limbs undergo rotation. How do the upper limbs rotate and how do the lower limbs rotate?
Upper limbs rotate 90 degrees laterally
Lower limbs rotate 90 degrees medially
Explain why the upper limbs develop before the lower limbs?
Due to blood supply. We like to shunt more blood and oxygen to the brain and on the way there is the Subclavian As. which take more blood to the upper extremity.
In development, this branches off the dorsal aorta.
Intersegmental Arteries
This comes off the Intersegmental Arteries and forms the Brachial A. and Median A. during development.
Primary Axial A.
***Median A. isn’t present in adults, there is remodeling
What does the Primary Axial A. give rise to that is important for the upper limb?
Brachial A.
What does the Primary Axial A. become for the lower limb?
Deep artery of the thigh
How does proximodistal growth occur with the limb bud mesoderm and the AER?
The limb-bud mesoderm signals FGF-10 to form the AER. The AER then in turn will signal FGF-4 and FGF-8 back to the mesenchyme (mesoderm). This constant signaling causes the proximodistal growth to occur.
For Dorso-ventral patterning, the dorsal surface is forming the extensors and maintained by _______, while the ventral surface is forming the flexors and is maintained by _______.
Wnt7
BMPs
Anterior-Posterior patterning (also known as Preaxial-Postaxial patterning) is established by what?
Zone of Polarizing Activity (ZPA)
***On posterior side of limb (little finger side)
What are the signals from the ZPA that specifically signal the posterior elements to form (3rd, 4th, 5th digits and ulna)?
SHH
Retinoic Acid
What would have to be lost to result in the loss of posterior elements (3rd, 4th, 5th digits and ulna)?
Loss of ZPA
What would occur in an upregulation of ZPA?
Additional posterior elements (polydactyly)
What would occur in a duplication of the ZPA?
Duplication of posterior elements (i.e., Little fingers on both sides of the thumbs)
T/F. Anterior elements (i.e., Radius/Thumb) are formed prior to Posterior elements (i.e., little finger/Ulna).
False. The Posterior elements are formed prior to the Anterior elements.
***Therefore, disruption of the Anterior-Posterior patterning growth can result in the loss of anterior elements (i.e., loss of radius and/or thumb)
During what week would a birth defect in the hands with upregulation of the ZPA occur (polydactyly)?
Week 6 – because this is when your forming digital rays of hands
During what week would a birth defect in the feet with duplication of the ZPA occur (polydactyly)?
Week 7 – because this is when your forming digital rays of feet
What causes syndactyly (fused fingers)?
Loss/not enough apoptosis of skin between fingers, which means there is a problem with the BMPs
***Remember syndactyly is common with Poland Syndrome!
During what week would the birth defect of syndactyly occur?
Week 8 – because this is when BMPs activate apoptosis of the skin between fingers to form separate digits
This is the term for the birth defect that occurs when part of a limb is missing.
Meromelia
This is the term for the birth defect that occurs when hands and/or feet are attached close to the body.
Phocomelia
Why does Phocomelia occur and in what week?
There is a problem with FGF signaling in the AER, making the Proximo-Distal patterning mess up.
Can occur in weeks 4-8
This is the term for when upper limbs do not form at all.
Amelia
Why does Amelia occur and in what week?
There is a problem with FGF signaling in the AER, making the Proximo-Distal patterning mess up.
Occurs in week 4 (very start of limb bud formation)
Forked/Split Hand or Foot, also called _________, can occur during week _____ for the hand and week ______ for the foot.
Ectrodactyly
6
7
Why does Ecrtodactyly occur?
The center of the AER did not develop properly or it degenerated.
This drug was given to expectant mothers to help with morning sickness, but it was found to cause severe limb deformities in their babies.
Thalidomide
This is the term for congenital joint contractors, that usually involves more than 1 joint. The causes are unclear, but thought to be due to:
- Neurological defects
- Muscular abnormalities
- Joint and contiguous tissue problems
- Fetal crowding
Arthrogryposis
