11/20 Embryology of the Limbs Flashcards
What is the embryonic origin of the initial limb bud?
mesenchymal core (derived from cells of somatopleuric
What tissue would be responsible for a failure of the apical ectodermal ridge?
Somatic mesoderm in limb bud induces distal ectoderm to differentiate into a thickened ridge
what is the apical ectodermal ridge
a thickening of tissue at the apical end of the limb bud as it develops around the first month and plays essential rle in outgrowth of limb.
what is the area that is adjacent to the Apical ectodermal ridge?
the progress zone
Where does muscle and cartilage begin to differentiate in the limbs?
Proximal to the progress zone.
what movement of mesenchymal cells would prevent differentiation into bone/cartilage of the limbs
The movement of mesnchymal cells out of the progress zone towards the body!
what cell migration would prevent the formation of muscles in the limbs?
The migration of myogenic cells from somitic myotome into limb mesechyme
How do we get bones in the arms?
condensation of mesenchyme cells (after leave the progress zone) in central core of limb bud into precartilage rod that differentiate to hyaline cartilage model of bone that become bone in a proximal to distal direction
How would a cell that gets pushed out of the progress zone early not develop correctly?
the time spent in the progress zone determines proximodistal identity of skeletal element
Problems in what molecular cell signals could lead to paddle hands instead of fingers?
BMP and Wnt signaling is done wrong…Wnt stops cell death, and BMP and Dickkopf1 will shut down Wnt to cause the formation of fingers instead of a paddle, so syndactily will occur if you don’t down regulate Wnt by BMP and Dickkopf1.
how do we end up with dermatomes and myatomes that wrap around the legs and arms (explain limb rotation)
In arms, hands do not rotate, but hte rest of the limb rotates dorsally by 90 degreess…putting the initially cranial structures, including extensor muscles into a dorsal (posterior) position. but in the legs the entire limb rotates ventrally or towards the bell by 90 degrees putting hte extensor muscles into a ventral or anterior position
dissruption of what tissue would lead to problems in epidermis and associated structures, motor and sensory innervation in the limbs
ectoderm
disruption in what tissue would lead to problems in dermis and skeleton, some tendons, ligaments connective tissue and blood vessels
lateral plate mesoderm
disruption in what tissue would lead to malformation in the muscles of the limbs
the somites.
Contrast the growth of sensory and motor neuron
We make many more sensory neurons then we need, they innervate what they run into, and the others die. The motor neurons always go to the same spot!
Describe the development of neurons in the limbs
The motor and sensory axons initially grow out segmentally in spinal nerves, then converge in brachial and lumbosacral, sensory grow out later, follow the motor, plexus project into limb in either a dorsal or ventral branch.
Describe body rotation and the development of the location of the extensor muscles
the extensors in the upper and lower limbs both start in the cranial position. then the triceps rotate 90 degrees back and the quads rotate 90 degrees forward to get the extensors to the final position
The Disruption of what tissue could lead to a malformation of dermis and skeletal components and ( minor contribute to ligaments, tendons, blood vessles nad connective tissue of the limbs etc.)
The somatic lateral plate mesoderm. or the somatopleure (as apposed to the splanchnopeure). The somatic lateral plate mesoderm is on the outside.
What is the bone formation method of limb bones?
develop from cartilage via endochondral ossification
How do joints develop in bones?
the bones start as a continous plate of cartilage, precartilaginous rods split by becoming dense, cells become fibroblast-like then connective tissue, then necrossis to form joint.
failure of what molecular signal would prevent the formation of the joint cavity?
influence of BMP-related protein (GDF-50) and Wnt-14 cause cells to die to form the joint cavity.
what would the cells on either side of the necrotic zone of a joint become?
the articular cartilage of course!
what molecular signal is connected to pseudoachondroplaasia?
Oligomeric Matrix Protein (COMP)
The origin of tendons and contractile cells of muscle…
from the somites!
the name of the myotome region of the somite that seems to be the source of tendons
the syndetome that is located just interior to the myotome that will become the limb muscles
the transplantation of this tissue to another region of the body would lead to the developent of another limb at that location
lateral plate mesoderm from brachial region
what molecular signal would be necessary for limb initiation? — stick a bead of it in and it will cause a limb developmetn
FGF ( a knock-out of FGF would be missing a limb or more!)
what molecular signal would be needed to make the lower vs. the upper limb?
Hox genes controlling where T-box transcrition factors are expressed…Tbx4 is for lower limb and Tbx5 is expressed in upper limb
what genes would alter limb postion?
Hox genes would move the limb around cranial to caudal position, and Tbx 4/5 would determine if it is a leg or arm!
what could lead to supernumerary limbs in humans?
anything that could increase the size of the domain of tissue where the limb comes from, i.e. increase the size of tissue area where the LPM is directing teh growth of a limb..
What tissue and what factor will determine a limb truncation and the location of that truncation?
Limb segments are specified in proximedistal direction from the Apical ectodermal ridge. AER removal truncates the limb and age of removal determines the proximodistal level of truncation
what molecular signal from the AER will direct the growth of the progress zone?
FGF!
the removal of FGF10 would do what to the developing limb?
it is normal y in the intermediate mesoderm and somites and leads to FGF8 in the AER and down stream the effect would be a truncadtio of the limb
removal of what signal from the progress zone would lead to a loss of proliferative state of the cells in that zone
FGF8
how could the AER in a developing limb be replaced by a simple moleculaar signal?
replace with FGF and you can still get some limb development (FGF10 to FGF 8 etc)
What temporal factor will determine the identify of limb segments?
the age of the mesoderm determines which limb segments form following heterochronic recombination of AER and progress zone meso derm
what is the molecular signal that will contribute to the proximodistal pattern of the limbs?
HOX genes
Describe the numeriical identification of HOX genes as you move down the arm and hand
the Hox genes responsible for development are hox 9,10,11,12,and 13 from the scapula to the fingers.
What molecuar singal could lead to a problem in craniocaudal axis determination (lead to extra fingers!)?
SONIC HEDGEHOG SHH secreted from region of posterior mesoderm called the zone of polarizing activity (ZPA)
how could you end up with an outward facing hand?
by reversing the ectoderm that is covering the mesoderm in the limb bud
what is the signal given off of the ectoderm that determens the dorsal/ventral orientation of the limb (upside down hands?)
the signal is Wnt7a from the dorsal side of the limb and En-1 from the ventral ectoderm!
