Musculoskeletal Embryology

Question 1

Embryo folding

Answer 1

Occurs between days 18-24 after fertilization, trilaminar embryo undergoes cranial-caudal and lateral folding

Question 2

After folding - endoderm

Answer 2

The yolk sac becomes the gut tube and is suspended in the body cavity, will become the epithelial lining of the gut

Question 3

After folding - mesoderm

Answer 3

Suspends gut tube within tube of the body and surrounds the gut tube, will become the wall of the gut. and under the ectoderm will become the components of the body wall and limbs

Question 4

After folding - ectoderm

Answer 4

Brought around the embryo with mesoderm to form anterior body wall and encase embryo in amniotic cavity, will become the epithelium of the skin

Question 5

Paraxial mesoderm

Answer 5

On either side of the neural tube, forms the axial skeleton and skeletal muscle in the body wall and limbs

Question 6

Intermediate mesoderm

Answer 6

Next to the the paraxial mesoderm

Question 7

Lateral plate mesoderm

Answer 7

Lateral to the intermediate mesoderm, divided into somatic mesoderm and splanchnic mesoderm

Question 8

Somatic mesoderm

Answer 8

In contact with ectoderm, and will form the connective tissue and smooth muscle of then body wall and limbs, as well as the appendicular skeleton

Question 9

Splanchnic mesoderm

Answer 9

In contact with endoderm, and will form the wall of the gut

Question 10

Limb development time and location

Answer 10

Between weeks 4-8 and from the lateral plate mesoderm

Question 11

Limb embryonic induction

Answer 11

Intermediate mesoderm produces FGF8, which induces lateral plate to produce FGF10, which induces overlying ectoderm to form the apical ectoderm ridge (AER)

Question 12

Apical ectodermal ridge

Answer 12

Thickened ectoderm, maintains proliferation of the progress zone (somatic mesoderm) by producing FGF4 and FGF8, promotes outgrowth of limb bud along proximal/distal axis (shoulder to fingers)

Question 13

Cells leaving progress zone

Answer 13

As the limb elongates they are no longer under the control of AER and stop dividing and differentiate into cartilage and bone

Question 14

Removal of AER

Answer 14

Results in distal truncation of the limb (meromelia or amelia)

Question 15

Direction cells of the limb proliferate

Answer 15

Proximal to distal pattern

Question 16

Selective loss of AER

Answer 16

How digits form, reduces amount of FGF in interdigital spaces, causing apoptosis and cessation of cell proliferation

Question 17

Zone of polarizing activity

Answer 17

Specialized mass of cells in base of limb bud that regulate development along cranial/caudal axis

Question 18

ZPA role in maintaining AER

Answer 18

Induced by FGF8, produces retinoic acid which initiates expression of SHH to regulate the anteroposterior axis

Question 19

Sonic hedgehog

Answer 19

Establishes gradient of homeobox gene expression across developing limb

Question 20

Hox genes

Answer 20

Transcription factors that define pattern of differentiation from thumb to little finger

Question 21

Polydactyly

Answer 21

Formation of extra digits due to transplantation of the ZPA or implantation of a Shh ectopically expressed in anterior limb bud (as well as the usual posterior expression)

Question 22

Two methods by which bones develop

Answer 22

Intramembranous or endochondral ossification

Question 23

Intramembranous ossification bones formed

Answer 23

Flat bones of the skull and bones of the face

Question 24

Intramembranous ossification mesenchyme cell characteristics

Answer 24

Loosely organized, mainly mesodermal embryonic tissue that will develop into connective and skeletal tissues (like blood and lymph)

Question 25

Intramembranous ossification mesenchyme cell differentiation

Answer 25

Into osteoblasts that produce primary or woven bone (irregularly arranged collagen fibers)

Question 26

Intramembranous ossification woven bone

Answer 26

Remodeled to lamellar bone (parallel alignment of collagen into sheets)

Question 27

Endochondral ossification bones formed

Answer 27

Long bones, vertebral column, pelvis, sternum, skull base

Question 28

Endochondral ossification mesenchyme cell differentiation

Answer 28

Into chondroblasts that produce a cartilage model

Question 29

Endochondral ossification cartilage

Answer 29

Becomes vascularized and is replaced by bone matrix

Question 30

Endochondral ossification remaining cartilage

Answer 30

Found at surface of epiphysis as articular cartilage, then between epiphysis and diaphysis as the epiphyseal plate

Question 31

Epiphyseal plate role

Answer 31

Regulates the growth in length of long bones

Question 32

Epiphyseal plate proliferation

Answer 32

Occurs at the epiphyseal side of plate, replacement by bone is on the diaphyseal side

Question 33

Epiphyseal plate bone growth duration

Answer 33

As long as the rate of cell division is equal to that of cell death and ossification, typically until the 20th year of life

Question 34

Somitomeres

Answer 34

Segments of paraxial mesoderm

Question 35

Somitomere mesoderm contributions

Answer 35

1-7 to the head and neck, the rest condense into somites

Question 36

Somites

Answer 36

Differentiate into sclerotome, myotome, and dermatome

Question 37

Sclerotome

Answer 37

Axial skeleton, formed by cells of the ventral and medial wall of somite that lose epithelial arrangement and migrate towards the notochord

Question 38

Dermomyotome

Answer 38

Remaining cells following sclerotome migration, will turn into dermatome and myotome

Question 39

Dermatome

Answer 39

White, dermis of skin

Question 40

Myotome

Answer 40

Red, skeletal muscle

Question 41

Myotome - two splits

Answer 41

Dorsal epimere, ventral hypomere

Question 42

Epimere

Answer 42

Develops into intrinsic back muscles

Question 43

Hypomere

Answer 43

Develops into limb and body wall muscles

Question 44

Dorsal and ventral condensation

Answer 44

Hypomere cells that migrate into the limb bud to become skeletal muscles of the limbs

Question 45

Dorsal condensation

Answer 45

Gives rise to extensor muscles

Question 46

Ventral condensation

Answer 46

Gives rise to flexor muscles

Question 47

Skeletal muscle differentiation cause

Answer 47

Caused by growth factors inducing the expression of transcription factors

Question 48

Skeletal muscle differentiation steps

Answer 48

Somatic epithelium, myogenic progenitor cells (mitotic phase), myoblast, myotube, myofiber with muscle satellite cells/stem cells (postmitotic phase)

Question 49

Growth factors in skeletal muscle differentiation

Answer 49

FGF, TGF-B

Question 50

Transcription factors in skeletal muscle differentiation

Answer 50

Myf-5, Pax-3

Question 51

Myf-5

Answer 51

Gives rise to Myogenin and MyoD

Question 52

Pax-3

Answer 52

Gives rise to MyoD

Question 53

MyoD

Answer 53

Gives rise to myoblast genes (actin, myosin) or myogenin

Question 54

Myogenin

Answer 54

Gives rise to myotube genes (troponin, tropo-myosin, etc) or MRF-4

Question 55

MRF-4

Answer 55

Gives rise to myofiber genes

Question 56

Axons of motor neurons

Answer 56

Enter limb bud in 5th week of development, grow into dorsal and ventral muscle masses

Question 57

Axons of sensory neurons

Answer 57

Enter limb bud after motor axons, supply dermatomes, which are areas of skin innervated by a single spinal nerve and its dorsal root ganglion

Question 58

Weeks 4-5

Answer 58

Most susceptible to teratogen induced limb malformations

Question 59

Three categories of human limb defects

Answer 59

Reduction defects, duplication defects, and dysplasia

Question 60

Reduction defect definition

Answer 60

Part of (meromelia) or entire limb (amelia) is missing, phocomelia is a type where hands of feet project directly from shoulder or hip

Question 61

Reduction defect example

Answer 61

Thalidomide (a teratogen) causes meromelia (at 5 weeks) and amelia (at 4 weeks)

Question 62

Critical period of limb development

Answer 62

24-36 days

Question 63

Reduction defect thalidomide mechanism

Answer 63

Disruption of the AER

Question 64

Duplication defect definition

Answer 64

Extra limb elements are present (polydactyly)

Question 65

Duplication defect mechanism

Answer 65

Duplication of the ZPA

Question 66

Dysplasia definition

Answer 66

Malformation of part of the limb (syndactyly)

Question 67

Dysplasia mechanism

Answer 67

AER doesn't break down between digits, so apoptosis doesn't occur normally when forming digits

Question 68

Syndactyly

Answer 68

Abnormal fusion of digits due to reduced apoptosis