10/10 Limb Development - Dennis Flashcards
What is musculature derived from?
paraxial mesoderm which produces myotomes
What are bones derived from?
lateral plate mesoderm from the somatic region
What are tendons derived from?
lateral plate mesoderm from the somatic region
At what point point are both limb buds present?
4th week
At what point do hand/feet plates appear>
5th week
At what point does chondrification begin?
5th week
At what point do the digital rays of hands appear?
6th week
At what point do we see a cartilaginous limb skeleton?
6th week
At what point do the digital rays of the feet appear?
7th week
At what point does osteogenesis begin?
7th week
At what point does limb rotation begin?
7th week
At what point do separate digits form?
8th week
At what point does primary ossification begin?
12th week
At what point does the upper limb bud form?
24 days
At what point does the lower limb bud form>
28 days
What developmental name is given to the humerus?
stylopod
What developmental name is given to the forearm?
zeugopod
What developmental name is given to the hand?
auto pod
What induces a limb bud to form? What kind of signalling is happening?
Fgf10 from lateral plate mesoderm activates Wnt
These Wnt’s then induce Fgf8 in the ectoderm (the growing part of the limb bud)
Fgf8 causes production of more Fgf10
This creates a positive feedback loop
What is proximal distal outgrowth of the limb bud controlled by?
Apical Ectodermal Ridge (AER)
What does the Apical Ectodermal Ridge secrete? (AER)? What is the function of the secretion?
Fibroblast growth factor 8 (FGF8)
FGF8 can mimic the AER by inducing supernumerary limbs
What Hox paralogs give rise to the stylopod?
Hox 9 - 10 Paralogs
What Hox paralogs give rise to the Zeugopod?
Hox 11 Paralogs
What Hox paralogs give rise to the Autopod?
Hox 12 - 13 paralogs
Define Paralog?
genes that are related to each other because they come from a common ancestral DNA sequence
Prior to limb bud outgrowth what is the one of the first directional restrictions seen?
Anterior posterior specification
What decides the overall shape and direction of the limb bud?
Zone of Polarizing Activity (ZPA)
What does the Zone of Polarizing Activity produce?
Sonic hedgehog (Shh)
If you were to remove a Zone of Polarizing Activity (ZPA) and implant it into an anterior limb bud what would you expect to happen?
duplicate digits to the limb buds own ZPA would appear because of the additional ZPA
What is the function of Bone Morphogenetic Protein (BMP)?
shapes our digits
High [BMP] leads to increased cell death (apoptosis)
Prior to limb rotation what is the orientation of the ventral and dorsal surfaces of a limb bud?
ventral surface faces medially
dorsal surface faces laterally
What does the dorsal muscle mass of a limb bud form?
upper limb –> extensors and suppinators
Lower limb –> extensors and abductors muscles
What does the ventral muscle mass of a limb bud form?
upper limb –> flexors and pronators muscles
Lower limb –> flexors and adductor muscles
How long does it take for a primary axial a. To establish itself in the limbs?
Upper limb - Day 30
Lower limb - Day 36
What is Meromelia? What causes it?
absence of part of a limb
Caused by late FGF signalling or partial loss of FGF signaling
What is Amelia? What causes it?
Absence of the entire limb
Caused by early loss of FGF signaling
What is Polydactyly? What causes it?
presence of supernumerary digits
Caused by overexpression of Shh (creation of a 2nd ZPA)
Adactyly vs. Syndactyly
Adactyly - absence of digits
Syndactyly - fusion of digits
What is Phacomelia? What causes it?
Thalidomide Baby
partial loss of FGF signaling or Hox disruption
What is Ectrodactyly?
“lobster claw”
split hand/foot deformity
What does Shh dictate?
The ventral portion of the neuraltube
What controls the dorsal-ventral axis?
Wnt7a - responsible for dorsal portion
Lack of wnt7A dictates ventral axis (and Shh)
What controls Wnt7a release (turns on)?
Lmx1b
Where do limb tendons arise from?
Lateral plate mesoderm
What artery branches of the aorta to join the primary axial a. Of the upper limb?
7th cervical intersegmental a.
What artery branches of the aorta to join the primary axial a. Of the lower limb?
5th lumbar intersegmental a.
