11/20 Embryology of the Limbs

Question 1

What is the embryonic origin of the initial limb bud?

Answer 1

mesenchymal core (derived from cells of somatopleuric

Question 2

What tissue would be responsible for a failure of the apical ectodermal ridge?

Answer 2

Somatic mesoderm in limb bud induces distal ectoderm to differentiate into a thickened ridge

Question 3

what is the apical ectodermal ridge

Answer 3

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.

Question 4

what is the area that is adjacent to the Apical ectodermal ridge?

Answer 4

the progress zone

Question 5

Where does muscle and cartilage begin to differentiate in the limbs?

Answer 5

Proximal to the progress zone.

Question 6

what movement of mesenchymal cells would prevent differentiation into bone/cartilage of the limbs

Answer 6

The movement of mesnchymal cells out of the progress zone towards the body!

Question 7

what cell migration would prevent the formation of muscles in the limbs?

Answer 7

The migration of myogenic cells from somitic myotome into limb mesechyme

Question 8

How do we get bones in the arms?

Answer 8

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

Question 9

How would a cell that gets pushed out of the progress zone early not develop correctly?

Answer 9

the time spent in the progress zone determines proximodistal identity of skeletal element

Question 10

Problems in what molecular cell signals could lead to paddle hands instead of fingers?

Answer 10

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.

Question 11

how do we end up with dermatomes and myatomes that wrap around the legs and arms (explain limb rotation)

Answer 11

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

Question 12

dissruption of what tissue would lead to problems in epidermis and associated structures, motor and sensory innervation in the limbs

Answer 12

ectoderm

Question 13

disruption in what tissue would lead to problems in dermis and skeleton, some tendons, ligaments connective tissue and blood vessels

Answer 13

lateral plate mesoderm

Question 14

disruption in what tissue would lead to malformation in the muscles of the limbs

Answer 14

the somites.

Question 15

Contrast the growth of sensory and motor neuron

Answer 15

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!

Question 16

Describe the development of neurons in the limbs

Answer 16

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.

Question 17

Describe body rotation and the development of the location of the extensor muscles

Answer 17

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

Question 18

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.)

Answer 18

The somatic lateral plate mesoderm. or the somatopleure (as apposed to the splanchnopeure). The somatic lateral plate mesoderm is on the outside.

Question 19

What is the bone formation method of limb bones?

Answer 19

develop from cartilage via endochondral ossification

Question 20

How do joints develop in bones?

Answer 20

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.

Question 21

failure of what molecular signal would prevent the formation of the joint cavity?

Answer 21

influence of BMP-related protein (GDF-50) and Wnt-14 cause cells to die to form the joint cavity.

Question 22

what would the cells on either side of the necrotic zone of a joint become?

Answer 22

the articular cartilage of course!

Question 23

what molecular signal is connected to pseudoachondroplaasia?

Answer 23

Oligomeric Matrix Protein (COMP)

Question 24

The origin of tendons and contractile cells of muscle…

Answer 24

from the somites!

Question 25

the name of the myotome region of the somite that seems to be the source of tendons

Answer 25

the syndetome that is located just interior to the myotome that will become the limb muscles

Question 26

the transplantation of this tissue to another region of the body would lead to the developent of another limb at that location

Answer 26

lateral plate mesoderm from brachial region

Question 27

what molecular signal would be necessary for limb initiation? — stick a bead of it in and it will cause a limb developmetn

Answer 27

FGF ( a knock-out of FGF would be missing a limb or more!)

Question 28

what molecular signal would be needed to make the lower vs. the upper limb?

Answer 28

Hox genes controlling where T-box transcrition factors are expressed…Tbx4 is for lower limb and Tbx5 is expressed in upper limb

Question 29

what genes would alter limb postion?

Answer 29

Hox genes would move the limb around cranial to caudal position, and Tbx 4/5 would determine if it is a leg or arm!

Question 30

what could lead to supernumerary limbs in humans?

Answer 30

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..

Question 31

What tissue and what factor will determine a limb truncation and the location of that truncation?

Answer 31

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

Question 32

what molecular signal from the AER will direct the growth of the progress zone?

Answer 32

FGF!

Question 33

the removal of FGF10 would do what to the developing limb?

Answer 33

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

Question 34

removal of what signal from the progress zone would lead to a loss of proliferative state of the cells in that zone

Answer 34

FGF8

Question 35

how could the AER in a developing limb be replaced by a simple moleculaar signal?

Answer 35

replace with FGF and you can still get some limb development (FGF10 to FGF 8 etc)

Question 36

What temporal factor will determine the identify of limb segments?

Answer 36

the age of the mesoderm determines which limb segments form following heterochronic recombination of AER and progress zone meso derm

Question 37

what is the molecular signal that will contribute to the proximodistal pattern of the limbs?

Answer 37

HOX genes

Question 38

Describe the numeriical identification of HOX genes as you move down the arm and hand

Answer 38

the Hox genes responsible for development are hox 9,10,11,12,and 13 from the scapula to the fingers.

Question 39

What molecuar singal could lead to a problem in craniocaudal axis determination (lead to extra fingers!)?

Answer 39

SONIC HEDGEHOG SHH secreted from region of posterior mesoderm called the zone of polarizing activity (ZPA)

Question 40

how could you end up with an outward facing hand?

Answer 40

by reversing the ectoderm that is covering the mesoderm in the limb bud

Question 41

what is the signal given off of the ectoderm that determens the dorsal/ventral orientation of the limb (upside down hands?)

Answer 41

the signal is Wnt7a from the dorsal side of the limb and En-1 from the ventral ectoderm!