Musculoskeletal Embryology

Question 1

What do embryonic genes determine?

Answer 1

The pattern of the body including that of the limbs

Question 2

What embryonic genes have roles in patterning and have been well characterized?

Answer 2

FGF, Qnt-7a, Shh, band Homeobox (Hox) genes

Question 3

When do limbs for after fertilization?

Answer 3

after then end of the 4th week as buds along the body wall and are pattered along 3 planes.

Question 4

What are the 3 planes of limb development?

Answer 4

proximal to distal, dorsal-ventral, anterior posterior

Question 5

What gene is proximal to distal limb development dependent on?

Answer 5

FGF (fibroblast growth factor) gene

Question 6

What produces the FGF protein in proximal to distal development?

Answer 6

the mesoderm causing proliferation of the ectoderm at the site where the limbs form

Question 7

What forms the apical ectoderm ridge (AER) in proximal to distal development?

Answer 7

proliferating ectoderm

Question 8

What does the AER begin to produce in proximal to distal development?

Answer 8

FGF causing proliferation of the mesoderm called the progress zone

Question 9

What happens with the AER in proximal to distal development is removed?

Answer 9

mesoderm stops proliferating and the limb stops growing but if you add back FGF you get normal growth

Question 10

How do digits form?

Answer 10

in proximal to distal limb development digits form when apoptosis occurs in the AER to separate it into 5 separate ridges, final separation of the digits is achieve by additional apoptosis in the interdigital spaces.

Question 11

Dorsal to ventral limb development is depended on what genes?

Answer 11

Want-7a it is a signaling protein expressed by the AER, it activates LMX-1 gene in the mesoderm causing it to form dorsal structures.

Question 12

What does deletion of the LMX-1 gene cause in dorsal to ventral limb development?

Answer 12

causes the limb to form with 2 ventral sides

Question 13

What does ectoderm on the ventral side of the limb bud express?

Answer 13

transcription factor Engrailed1 which represses Wnt-7a expression on the ventral side of the limb

Question 14

What makes the dorsal side of the limb dorsal and the ventral side ventral

Answer 14

presence of Wnt-7a dorsal and absence of Wit-7a ventral

Question 15

What gene does anterior-posterior development depend on?

Answer 15

Shh (sonic hedgehog) gene

Question 16

What is Shh (sonic hedgehog) gene?

Answer 16

a signaling protein produced at the posterior base of the limb buts .

Question 17

What cells produce Shh?

Answer 17

zone of polarizing activity (ZPA)

Question 18

What results in mirror image duplication of limb structures?

Answer 18

transplantation of the ZPA or implantation off a Shh bead to the anterior side of the limb bud

Question 19

When Shh diffuses across the limb bud it activates the expression of what family of transcription factors?

Answer 19

Homeobox (Hox) gene

Question 20

What is a Hox gene?

Answer 20

Hox genes define the pattern of differentiation from the thumb (anterior or cranial) to little finger (posterior or caudal) as well as segmental organization of the entire embryo in a cranial to caudal direction

Question 21

How does bone develop?

Answer 21

Either intramembranous (membranous or dermal) or endochondral ossification

Question 22

What bones are formed by intramembranous ossification?

Answer 22

flat bones of the skin and bones of the face

Question 23

What do mesenchyme cells differentiate into in intramembranous ossification?

Answer 23

directly into osteoblasts.

Question 24

What is mesenchyme?

Answer 24

loosely organized tissue mainly mesodermal tissue that develops into connective and skeletal tissue including blood and lymph

Question 25

What type of bone do osteoblast lay down?

Answer 25

primary or woven bone (irregularly arranged collagen fibers) that is removed Ito lamellar bone (parallel alignment of collagen into sheets)

Question 26

What bones are formed by endochondral ossification?

Answer 26

long bones and vertebral column, pelvis, sternum and skill base

Question 27

In endochrondral ossification mesenchyme differentiates into what?

Answer 27

chondroblasts which produce a cartilage model. cartilage becomes vascularized bringing in osteoblast and restricting proliferating chondrocytes to the ends (epiphysis) of the bone.

Question 28

What is the region called between the epiphysis and diaphysis where the bone grows in length?

Answer 28

epiphyseal (growth) plate or the physics

Question 29

During endochrondral ossification where does proliferation occur?

Answer 29

the epiphyseal side of the plate (zone of proliferating cartilage). Chondrocytes towards the shaft side (diaphysis) undergo hypertrophy and apoptosis (zones of hypertrophic cartilage) as they mineralize the surround matrix (zone of calcified cartilage)

Question 30

Where do osteoblasts bind during endochrondral ossification?

Answer 30

bind to the mineralized matrix and deposit bone matrix (zone of ossification).

Question 31

The long bone will continue to go as long as....

Answer 31

the rate of proliferating equals the rate of cell health and ossification

Question 32

Where does skeletal muscle develop from?

Answer 32

mesoderm closest to the notochord and neural tube, called the paraxial mesoderm.

Question 33

The paraxial mesoderm becomes organized into segments that form what?

Answer 33

craniocaudal sequence

Question 34

Segments in the head and neck from the carniocaudal sequence are called?

Answer 34

somitomeres

Question 35

Segments in the trunk from the carniocaudal sequence are called?

Answer 35

somites

Question 36

What doe the smites differentiate into?

Answer 36

axial skeleton, all skeletal muscle and some of the dermis of the skin

Question 37

During the 5th week of development what do the axons of motor neurons do?

Answer 37

axon of the motor neurons from the spinal cord enter the limb bud and now into the developing skeletal muscles at the same segmental level.

Question 38

When do axons of sensory neurons enter the limb bud?

Answer 38

after the motor axon and supply the segmental regions of the skin.

Question 39

What is a dermatome?

Answer 39

it is an area of skin innervated by a single spinal nerve and its dorsal root ganglion.

Question 40

As the limbs grow in length what happens to the original segmental dermatome?

Answer 40

The pattern changes

Question 41

During 6-8 weeks in development how do limbs rotate?

Answer 41

lower limbs medially rotate and the upper limbs laterally rotate causing the dermatomes to spiral down the limb, especially the lower limb.

Question 42

What are the 3 categories of limb defects in humans?

Answer 42

reduction defects, duplication deficits, dysplasia

Question 43

What are reduction defects?

Answer 43

are when part of (meromelia) or the entire limb (amelia) is missing, phocomelia is a type of mermelia when hands or feet project directly from the shoulder or hip.

Question 44

What are duplication defects?

Answer 44

when extra limb elements are present. Polydactyly (extra digits)

Question 45

What are duplication defects?

Answer 45

is a malformation of part of the limb, example of this is abnormal fusion of the digits resulting from reduced apoptosis (syndactyly).