Limb Embryology

Question 1

During what time is an enbryo most susceptible to birth defects by teratogens?

Answer 1

from weeks 4 to 8

this is when the major organ systems are all developing

if the exposure is before this, the likihood is much higher for spontaneous abortion

Question 2

What does the notochord induce in the ectoderm at week 3-4?

Answer 2

It induces the ectoderm to invaginate, forming the neural groove and tube

Question 3

What will the notochord eventually develop into?

Answer 3

the vetrebral bodies and intervertebral discs

Question 4

Besides signalling the formation of the neural groove/tube and contributing to the spinal cord, what does the notochord do?

Answer 4

1. defines the axes of the embryo
2. mechanical role in the foldin gprocess

Question 5

What develops on either side of the notochord?

what signals their formation?

Answer 5

the paraxial mesoderm gives rise to somites

their formation is signalled by the neural tube

Question 6

The lateral mesoderm separates into what two layers? WHat is between them?

Answer 6

the somatic and the splanchnic lateral mesoderm

separated by the intraembryonic ceolom

Question 7

What is embryonic connective tissue called? WHat is it derived from?

Answer 7

mesenchyme

it’s derived from mesoderm and neural ccrest cells

Question 8

What will mesenchymal cells differentiate into?

Answer 8

into myoblasts, chondroblasts, osteoblasts and fibroblasts (multipotenti)

Question 9

What are somites called before they’re “mature” somiates?

Answer 9

somitomeres - they’re clusters of mesodermal tissue that appear segmentally in rostral ot caudal progression, derived from parazial mesoderm

Question 10

WHy is week 4 such a critical period in development?

Answer 10

the neural tube begins to close and you get cephalo-caudal and lateral folding

this is also when you start developing the somites, organ systems, phanygenal arches, ear and eyes, and limb buds begin to appear

Question 11

WHere in the embryo do the somitomeres NOT mature into somites?

Answer 11

the first 7 pairs - they will contribute mesoderm to the head and neck region (the next 35 will become somites)

Question 12

THe somites become segmented into what two sets of cells?

WHat happens in the next division?

Answer 12

Somites divide into sclerotome (ventromedially toward notochord and neural tube) and dermomyotome (lateral portions)

THen the dermomyotome divides into the **myotome ** and dermatome (which will be right under the ectoderm)

Question 13

What does the sclerotome develop into? THe dermatome? THe myotome?

Answer 13

sclerotome = bone and some CT

myotome = muscle

dermatome = dermis and hypodermis (epidermis is ectoderm)

Question 14

WHat are the two types of developmental bone formation?

Answer 14

membranous bone formation

endochondral bone formation

Question 15

Describe membranous bone formation

Answer 15

mesenchyme condenses into vascular CT

the mesenchymal cells produce collagen fiber matrix

the cells differentiate into osteoblasts

the osteoblasts lay down mineralized bone matrix

Question 16

Wher ein the body does membranous bone formation occur?

Answer 16

in the flat bone sof the skull

Question 17

Describe endohcondral bone formation.

Answer 17

It’s when hyaline cartilage is laid down first, and is then replaced by bone…..

THe mesenchymal cells differentiate into chondroblasts (instead of osteoblasts) and lay down a hyaline cartilage model of the long bones.

the matrix calcifies around the periphery of the shaft.

On the interior, some cells differentiate into osteoblasts and beging to lay down mineralized bony matrix (the primary ossification center)

BLood vessels invade and stimulate ossification

the diaphysis grows in length toward the ends of the bone

A 2nd ossification center forms in the piphyses and lay down bone in the opposite direction toward the primary ossification center.

Question 18

What is the space of hyaline cartilage located between the primary and secondary ossification centers called?

Answer 18

the epiphyseal growth plate

Question 19

WHen do primary ossification centers appear during development?

WHen do secondary ossification centers appear?

Answer 19

primary - during week 8 of development

secondary - after birth

Question 20

What happens when there is no more hyaline cartilage between the ossification centers?

Answer 20

the epiphyseal plate has closed and the bone won’t grow anymore

Question 21

Loose mesenchyme between the cartilage models of bones differentiate into what?

Answer 21

either fibrous tissue or fibrocartilage depending on the type of joint

Or in the case of synovial joints, programmed apopotsis results in the joint cavity between the adjacent cartilage models

Question 22

What is marfan syndrome?

Answer 22

it’s a connective tissue disorder that causes excessive long bone growth

It’s related to the fibrillin gene

you get long thin limbs

it also affects the heart, vessels, bones lungs, and eyes

Question 23

What is osteogenesis imperfecta?

Answer 23

It’s a defect in type 1 collagen gene

autosomal dominant or recessive

you get extreme bone fragility because you don’t have the colagen to provide resilience for the bone

results in frequent fractures and hypermobile joints and decreased bone density

Question 24

What happens in achondroplasia?

Answer 24

It’s a defect in FGFR3 so that you get a mutated form of the receptor that is actively involved bone growth of long bones

can be autosomal dominant or spontaneous mutation

it’s the most common form of dwarfism

Question 25

What happens in acromegaly?

Answer 25

excess growth hormone AFTER growth plates have closed, resulting in large, heavy bones especially the face hands and feet (Andre the giant)

Question 26

What happens in gigantism?

Answer 26

when you have excess growth hormone during childhood BEFORE the growth plates have closed you get overal large size - height AND organs

Question 27

What happens in congenital hip dysplasia?

Answer 27

It's incomplete formation of the acetabulum, which holds the femur head into the hip joint you end up with legs held in positions that don't match, less movement, uneven leg length - can be complete dislocation or just laxity

Question 28

The skeletal system is divided into what two classifications?

Answer 28

the axial skeleton and the appendicular skeleton

Question 29

what make sup the axial skeleton? the appendicular skeleton?

Answer 29

axial: skull, vertebral column, ribs, and sternum appendicular: pectoral and pelvic girdles plus limbs

Question 30

What cells form a sheath around the notochord and neural tube?

Answer 30

sclerotome cells from the somites

Question 31

THe sclerotome from each somite divides into what to segments?

Answer 31

a loose CT segment and a dense CT segment

Question 32

What separates the dense and loose CT segments of the sclerotome?

Answer 32

von ebner's fissures

Question 33

As the sclerodermal cells converge, what do they form?

Answer 33

the centrum of the vertebral body

Question 34

During development, the cells in each of the sclerotomes segments migrate where? WHat does this mean for the composition of individual vertebrae?

Answer 34

They migrate away from the von Ebner's fissures, thus each vertebrae has a component from two somites

Question 35

what will pass through the von Ebner's fissures?

Answer 35

the spinal nerves

Question 36

What composes the occiput and what does this mean for cervical spinal nerves?

Answer 36

The occiput is made of the caudal prt of occipital 4 and the cranial part of cervical 1 this is why the C1 spinal nerves come sout ABOVE the C1 vertebra and why the C8 spinal nerve lies beneath the C7 vertebra (on top of the T1 vertebrae) After the cervical region, all of the spinal nerves run UNDER the vertebra of the same number

Question 37

The mesenchyme lying between the cephalic and caudal parts of the original sclerotome segmetns will fill the space surrouding the notochord and become what?

Answer 37

the annulus fibrosis of the intervertebral disc

Question 38

WHat will form the nucleus pulposis of the intervertebral disc?

Answer 38

the notochord

Question 39

How is the rest of the vertebra formed?

Answer 39

There is also condensation of slcerodermal cells surrounding the neural tube so that there is a cartilaginous structure with processes of hyaline cartilage called the **costal processes** Multiple ossification centers form in these costal processes and the neural arch these ossification centers will grow to form the pedicles, lamina and transver/spinous processes

Question 40

WHere does the ribs form off ot?

Answer 40

the costal processes - at first it's solid, but then costovertebral synovial joints form

Question 41

What forms the sternum?

Answer 41

the fusion of multiple ossification centers of sternebrae

Question 42

WHat are the 3 forms of spinal bifida?

Answer 42

spina bifida occulta meningocele myelomeningocele

Question 43

What happens in spina bifida occulta? WHat can you see on the outside?

Answer 43

In spinal bifida occulta the neural tube doesn't close properly so the neurla rch can't form and the vertebrae don't form. In the lumbosacral area the tube doesn't close so the vertebrae don't form right, but the spinal cord and meninges are intact so there isn't usually any defects you just get a tuft of hair in that region fo the back

Question 44

What happens in a meningocele? In a myalomeningocele?

Answer 44

meningocele: again, you don't get formation of the neural arch and the meninges bulgeout and fill with liquid - this you can see from the outside In a myelomeningocele, the spinal cord bulges out into the meningocele - definitely defects

Question 45

What happpens in Klippel Feil Sydrome?

Answer 45

it's congenital fusion of any of the cervical vertebrae, resultin gin brevicollis (short neck) and often scoliosis There are often abnormalities in the organ systems as well including heart ,kidney, rib and palate abnormalities

Question 46

What will a hemivertebra cause?

Answer 46

congenital scoliosis if there is only one chondrification/ossification center that forms in the vertebral body, you only get formation of it on on side and this causes the rest of the vertebra to angle around it, resultin gin scoliosis

Question 47

What is the result of a cervical rib?

Answer 47

thoracic outlet syndrome You get an extra rib growing in the cervical region (usually off C7), which compresses the brachial plexus and the axillary artery, so you get numbness, tingling, palor and pain in the arm

Question 48

What is pectus excavatum?

Answer 48

excessive growth of the connective tissue during sternum development where the area over the sternum poke inward can be so severe that it compresses the heart and/or lungs

Question 49

WHen do upper and lower limb buds occur during development?

Answer 49

upper limb buds on day 26 lower limb buds on day 28

Question 50

At what point in development are limbs no longer susceptible to teratogen exosures?

Answer 50

up to week 8

Question 51

What layer do the limb bud off from?

Answer 51

the lateral somatic mesoderm layer - it's mesenchymal tissue that will proliferate and differentiate upper limb - from next to the somites related to C5-T1 lower limb from L2-S2

Question 52

What gene controls the location of lumb buds?

Answer 52

homeobox genes (Hox)

Question 53

In limb formation, there is a thickening of the ectoderm layer of the distal border called the...

Answer 53

apical ectodermal ridge (AER)

Question 54

How does the apical ectodermal ridge affect limb formation?

Answer 54

They induce proliferation of undifferentiated mesenchymal cells using fibroblast growth factors in the adjacent progress zone. this is what causes lengthening of the limbs - it happens at the distal end

Question 55

At what end of the limb does cartilage/muscle differentiation start?

Answer 55

at the proximal end the AER keeps the distal end from differentiating until the very end so you can continue to get limb lenghtening

Question 56

WHat are the steps for developing the bones of the limbs? WHat kind of bone formation is this?

Answer 56

1. mesenchymal differentate into chondroblast 2. lay down hyaline cartilage model 3. mineralized bone 4. osteoblasts lay down hard bone this is endochondral bone formation

Question 57

What is the zone of polarizing activity and what does it do?

Answer 57

It's a region proximal to the apical ectodermal ridge along the posterior side of the limb. It's where the sonic hedgehog gene is activated to produce Shh proteins the Shh proteins will differentially affect the tissue closer to the ZPA than those further away this is what determines where the thumb and the pinky go! - controls anteroposterior axis of the limb

Question 58

How does diigt formation occur?

Answer 58

the limb buds flatten into paddle-shaped hands and feet you then get apoptosis in the AER that separates the paddle into 5 digits the patterning along the anteroposterior axis (thumb vs. pinky) is acontrolled by Shh from the ZPA

Question 59

In addition to lengthening, what do the limbs have to do?

Answer 59

rotate by 90 degrees the upper limbs rotate 90 degrees laterally to put the thumb lateral the lower limb roates 90 degrees internally so the great toe is medial

Question 60

WHat does this limb rotation mean for the dermatoms?

Answer 60

the dermatomes start out parallel along the limb, but wiht the rotation they also rotate and overlap each other. THey're not parallel anymore

Question 61

How can the limb rotation explain the funkiness of the brachioradialis?

Answer 61

the brachioradialis if a flexor muscle that originate on the posterior side and is innervated by the radial nerve - the extensor nerve!

Question 62

What does thalidamide cause?

Answer 62

it was a med given to mothers with morning sickness It caused limb deformities in the babies If exposed in week 4 = amelia (no limb) If exposed in week 5 = meromelia (pertial absence of limbs) or phocomelia (having paddle-like appendages attached almost directly to the torso)

Question 63

What is thalidomide used for now?

Answer 63

treatment of leprosy

Question 64

What is polydactyly?

Answer 64

It's th most common hand anomaly - you get an extra digit that may be fully formed or just soft tissue

Question 65

What is syndactyly?

Answer 65

You don't get proper apoptosis between the digits, so you get fully formed digits that are fused together.

Question 66

What is ectrodactyly?

Answer 66

lobster claw deformity it's due to an absent central digital ray, so you get a deep cleft between the digits - sometimes only 2 digits will form.

Question 67

How can muscles have innervation from multiple spinal segments?

Answer 67

fusion of myotomes - each myotome is associated with a neural tube segment

Question 68

What do the mesenchym cells differentiate into in myotomes?

Answer 68

spindle-shaped myoblasts which fuse to make myotube which develop myofilaments within their cytoplasm

Question 69

Myoblasts fuse to form what?

Answer 69

lon multinucleated myofibers that make up skeletal muscle

Question 70

Where will myotomes migrate?

Answer 70

some will go dorsally and others will migrate laterally around the body wall

Question 71

As the myotome differentates from the dermotome, it divides into two more segments....

Answer 71

1. the epimere/epaxial segment (smaller, more dorsal) 2. the hypomere/hypaxial segment (larger)

Question 72

What does the epimere form? Innervated by what?

Answer 72

the deep back muscles innervated by the dorsal primary rami

Question 73

what does the hypomere form?

Answer 73

neck flexors, vetrebral column flexors, the three concentric muscle layers of the thorax/abdomen supplied by the primary ventral rami

Question 74

The hypaxial myoblasts surround the developing long bones to form what two muscle groups? Innervated by what?

Answer 74

an extensor and a flexor group extensors supplied by the posterior division fo the ventral rami flexors supplied by the ventral divisions (lateral and medial cords)

Question 75

Why does the pectoralis major muscle still get innervation from the ventral fibers egen though it's technically not a limb flexor?

Answer 75

it develops from the hypomere anterior to the limb buds

Question 76

WHat is poland syndrome?

Answer 76

it's a congenital malformation or absence of the pectoralis major muscle on one side (usually the right) it often includes ipsilateral webbing of the fingers

Question 77

What happens in prune belly syndrome?

Answer 77

poor development of the abdominal muscles causing the skin to wrinkle over the unprotected abodminal organs also undescended testicles and UTI problems

Question 78

Where does the GI smooth muscle develop from?

Answer 78

the splanchnic mesoderm