Limb Development

Front 1

Describe phase 1 of limb development, establishment of the limb field. What type of tissue is invovled?

Back 1

The limbs fields develop from somatic mesoderm. The differential expression of Hox genes locates the upper field at the juction between cercvical and thoracic somites and the lower at the junction between thoracic and sacral. Tbx5 is expressed in the upper limb, Tbx4 and Pitx-1 are expressed in the lower limb

Front 2

Describe phase 2 of limb development, limb budding. Where do the signals initiate?

Back 2

Limb bud outgrowth is initiated by signaling molecules originating in the intermediate mesoderm. The signals induced expression of FGF10 in the apporpriate areas of lateral plate mesoderm resulting in limb bud outgrowth

Front 3

which embryonic tissues form skeletel elements, fibrous CT, and the dermis of the skin

Back 3

somatic mesoderm

Front 4

which embroynic tissues form hte epidermis of the skin

Back 4

surface ectoderm

Front 5

Which embryonic tissues for skeletal muscle in the limbs

Back 5

somitic (somite derived) mesoderm

Front 6

Describe the formation of the APical Ectodermal ridge

Back 6

Production of FGF-10 by the mesenchyme cells (from the somatic mesoderm) intiates scretion of FGF 8,2, and 4 in the distal ectoderm. this leads to a thickened ridge of ectoderm, the Apical Ectodermal Ridge

Front 7

Along which axis do the limbs elogate and limb segments form?

Back 7

proximal-distal

Front 8

Along which axis to muscles and nerves organize?

Back 8

dorsal-ventral

Front 9

Along which axis do the digits arrange

Back 9

anterior-posterior

Front 10

describe phase 3 of limb development-elongation

Back 10

The AER acts as a signaling center for the underlying mesenchyme of somatic mesoderm origin.This mesenchyme is refered to as the progress zone. Signals from the AER cause the progress zone mesenchyme to proliferate which causes the limb to elongate. The mesenchyme in the ZPA secretes Shh which maintains AER function until all limb segements are formed

Front 11

Phase 4 of limb development invovles tissue formation and organization which begins during the 5th week. How are the cartilage and bones formed? Muscles? Nerves?

Back 11

Somatic mesoderm condenses to form cartilage and bone models of limb bones, somite derived mesoderm migrates into the limb to form skeletal muscles. Motor axons of spinal nerves ender the limb. Guidence cues for muscle and nerve development are received by somatic mesoderm at the base of the limb bud

Front 12

What would happen to a limb if the AER was removed

Back 12

Development of the limb is stopped at that point, trucation

Front 13

What would happen to a limb if an additional AER was placed in

Back 13

Duplication of the limb structure occurs beginnin g from the time the graft is put in place

Front 14

What would happen to a limb if mesoderm other than limb bud mesoderm is placed adjacent to the AER

Back 14

Limb development is truncated. This suggests that only limb mesoderm is competent to respond to signals from the AER

Front 15

What would happen if mesoderm from the lower limb is placed adjacent to the AER of the upper limb

Back 15

Lower limb strucures develop suggesting that limb bud mesoderm is programmed to the axial level

Front 16

Describe the inductive interactions that occur between the AER and the progress zone

Back 16

The somatic mesoderm of the limb bud produces FGF10 which induces formation of the AER. The AER then produces FGF 8, 4, and 2 which maintains FGF 10 production in the somatic mesoderm adjacent to the AER promoting mesenchyme cell proliferation while inhibiting differentiation. The ZPA produces Shh which maintains FGF 8 secretion by the AER until all limb segments are formed

Front 17

What is the fate of the limb bud somatic mesoderm (progress zone)

Back 17

cartilage models of limb bones, fibrous CT, superficial fascia and dermis of skin

Front 18

WHere is the Zone of Polarizing activity located

Back 18

the ZPA is a group of somatic-mesoderm derived mesenchymal cells along the posterior border of the limb

Front 19

What does the zpa secrete? What is it's role

Back 19

The ZPA secretes Shh and RA which influence patterning along the anterior-posterior axis. The signaling induces the asymetric, nested expression of Hox genes that mediates the pattern for digit locatino along the AP axis of the limb bud

Front 20

Grafting a second ZPA into the anterior border of a limb bud would result in...

Back 20

a mirror image duplicaon of the digits in the distal segment of the limb

Front 21

Which border of the limb does the large digit develop? Small?

Back 21

The large digit develops along the cranial/preaxial border of the limb, the small along the caudal or postaxial border.

Front 22

What is the role of apoptosis in limb development?

Back 22

Separation of the ditial rays in the distal limb bud by causing breakdown of the AER in the interdigital region. The AER remains intact at the tips of each digit unti lthe correct length and number of phalanges is acheived. Apoptosis is also responsible for the absence of the distal phalanx in the large digit.

Front 23

Along which axis does patterning of the limb into comparments occur

Back 23

dorsal-venral, the compartments contain specific groups of muscles, nerves, and vessels

Front 24

How is limb patterning/ compartmentalization mediated

Back 24

Gradients between dorsal and ventralizing signals. Dorsal-Wnt and radical fringe cause Lmx-1 expression in the dorsal mesenchyme, Ventral-engrailed-1 expression prevents Lmx-1.

Front 25

Signals from which 'side" of the ectoderm maintain Shh prodcution by the ZPA

Back 25

dorsal

Front 26

Which mesoderm from which somite levels gives rise to the skeletal muscles in the limbs

Back 26

Upper-C5-T1, Lower L4-S3

Front 27

Where are muscle patterning siganls to the somitic mesoderm derived from

Back 27

somatic mesoderm that forms the fibrous CT associated with the muscle groups

Front 28

What are the "guidence cues" for neural structurs migrating into the limb received from?

Back 28

Mesenchyme cells at the base of the limb buds

Front 29

Describe the development of the vascular system in the limbs

Back 29

Sprouts from intersegmetal ateries at specific axial levels form a vascular plexus. Extensive remodeling occurs to form the final vascular pattern. The venous channel on the preaxial border bcomes the cephalic vein in the upper limb and the greater saphenous vein of the lower limb.

Front 30

Which direction do the limbs rotate

Back 30

The upper limb rotates laterally, the lower limb rotates medially.

Front 31

Describe the malformation that would result from a failure of formation of limb parts of the transverse type

Back 31

amelia/ meromelia, there is truncation/amputation along the proximal-distal axis resulting in missing distal parts

Front 32

Describe the malformation that would result form a fialure of formation of limb parts of the longitudinal type

Back 32

Meromelia. Absences of limb parts along the anterior-posterior axis (ie mssing radius and digits 1,2,3 or ulna and digits 4,5)

Front 33

Describe oligodacytly

Back 33

Failure of formation-longitudinal type. Limb structures are mssing from the media portion of the distal limb segement=> lobsert claw deformity

Front 34

Describe Phocomelia

Back 34

Failure of formation-longitudinal type. A more proximal segment is attached to the girdle and the intervening segment is missing

Front 35

Describe syndactly

Back 35

failure of differntiaon of limb parts, complete or partial fusion of one or more digits, failure of interdigital apoptosis

Front 36

Describe sirenomelia

Back 36

failure of differntation of limb parts, fused legs. May result from fused limb fields or abnormal development of the tailbud

Front 37

Describe polydactyly

Back 37

Duplication of limb parts, be inherited AD or AR, duplication of digits

Front 38

Describe Diplopia

Back 38

Duplication of limb parts-duplication of distal segmetn of limb, may involve formation of extra digits arranged in mirrior image, may result from duplication of the AER during limb elongation

Front 39

Describe congenital constriction band syndrome

Back 39

pieces of amion break away and wrap arond forming limb, can cause aputation. Note this is a deformation not a defect

Front 40

Club foot describes deformities of which bone

Back 40

talas

Front 41

Describe the position of the foot in Talipes Equinovarus

Back 41

the limb is bent toward the midline. The foot is plantar flexed, inverted, and adducted. The navicur, calcaneus, and cuboid ones are dispalced around the talus.

Front 42

What is the cause of club foot

Back 42

actual cause unknown, may have multifactorial inheritence, may be deformation due to uterine pressure when foot placement is abnormal , increase incidence linked to smoking

Front 43

Describe developmental dysplasia of the hip

Back 43

Hip joint is easily dislocated, may be underdevelopment of the femoral head of hip soket, may be accompaneid by general joint laxity and breech births. Maternal hormones may contribute.

Front 44

Describe cleidocranial dysplasia

Back 44

Hypoplasia or absence of the clavicles, usually bilateral and accompanied by other anomalies. Large head, small face, long neck, drooping shoulders, short, narrow chest. Delayed fontanelle closure and incomplete pubic development. Short fingers and dental problmes. Autosomal dominant inheritance, Runx-2 gene affected

Front 45

Describe the Sprengel deformity

Back 45

Undescend scapula, located at C4-T2. usually left but can be bilateral. Muscles are hypoplatic or atrophic, limited shoulder movement and disfigurment. Associated with vertebral anomalies, absent or fused ribs, Klipple-Fiel sequence and scoliosis