Development of the limbs

Question 1

What do somatic mesoderm and somites become?

Answer 1

somatic mesoderm –> limb skeleton

somites –> limb musculature

Question 2

When do limb buds appear? Where do they appear?

Answer 2

appear at the end of week 4
lower limbs 2 days behind upper limbs
appear on ventro-lateral body walls, extend ventrally (belly)

Question 3

How do limb buds elongate?

Answer 3

through proliferation of mesenchyme core (flexibl mesoderm)

Question 4

What is apical ectodermal ridge (AER)? Where is it located and what is its purpose?

Answer 4

orchestrates limb development: proximal to distal
keeps mesenchyme immediately underlying it undifferentiated
undifferentiated mesenchyme proliferates –> elongation
proximal mesenchyme begins to differentiate as it is far from AER - can’t receive molecular signal to stay undifferentiated

located at apex of mesenchyme core

Question 5

What does AER induce and what does it mark?

Answer 5

induces development of digits in hand/foot plates
AER marks the boundary between dorsal & ventral limb ectoderm - ‘dorsalventro patterning’
ectoderm exerts dorsalising & ventralising morphological changes over the mesenchyme core

Question 6

What are the 3 degrees of symmetry?

Answer 6

1. top & bottom: proximal –> distal
2. front & back: dorsal –> ventral
3. side to side: anterior –> posterior

Question 7

What is the apical ectodermal ridge (AER)?

Answer 7

thickened ectoderm at the apex of limb bud

Question 8

How does limb bud elongate?

Answer 8

through proliferation of mesenchyme core

Question 9

What is the zone of polarising activity (ZPA)?

Answer 9

a signalling centre at the posterior base of the limb bud
generates asymmetry in the limbs (anterior - posterior axis determination)
controls patterning (separate dorsal & ventral) & maintains AER

Question 10

Which component controls which axial specification?

Answer 10

Anterior - Posterior: ZPA (zone of polarising activity)
Proximal - distal: (AER) apical ectodermal ridge
D-V: ectoderm (dorsal & ventral)

Question 11

Describe the embryo’s axis

Answer 11

top-bottom: anterior - posterior
belly-back: ventral - dorsal
away-close: distal - proximal

Question 12

Describe an adult’s axis

Answer 12

top-bottom: superior - inferior
front - back: anterior - posterior
close - away: proximal - distal

Question 13

Hand & foot plates: what are digital rays? which process is required?

Answer 13

mesenchyme condensation (regress) within plates - cartilaginous models of digital bones formed (digital rays - flaring of limb buds = digits)
apoptosis require of tissue between digits (sculpts interdigital space)
AER only maintained over tips of digits, other break up to prevent proliferation between digits

Question 14

What is the purpose of apoptosis in hand & foot plates?

Answer 14

to sculpt interdigital space

Question 15

How are bones formed?

Answer 15

signals from AER to remain undifferentiated stop
lateral plate mesoderm condenses & differentiates
cartilage model forms
endochondral ossification (long bones) - osteoblasts - primary ossification centre in diaphysis of long bones

Question 16

Further development of long bones? (after birth)

Answer 16

secondary ossification centres appear in the epiphysis

bone growth is maintained by epiphyseal growth plate (cartilage forming regions)

Question 17

Compartmentalisation of muscles & its positional changes during development

Answer 17

myogenic precursors from somites migrate into limbs
coalesce into 2 common muscle masses around the newly formed skeletal element (ventral: flexor, dorsal: extensor)
individual muscles split (branch) from common masses

Question 18

Rotation of limbs

Answer 18

limbs extend ventrally at first, but as they elongate, they rotate
upper limb: rotates LATERALLY (thumb)
lower limb: rotates MEDIALLY (big toe)

Question 19

Describe the position of the limbs before and after rotation

Answer 19

before rotation: upper: thumbs up and elbows out
after rotation: thumbs out and elbows in

before rotation: lower: soles facing in, knees out
after rotation: soles facing down, knees up

Question 20

Limb innervation of upper & lower limb buds

Answer 20

upper LB: appears OPPOSITE caudal cercival spinal spinal segments (highest 2)

lower LB: appears OPPOSITE lumbar & sacral spinal segments (lowest 2)

Question 21

When do spinal nerves enter the limb bud? why?

Answer 21

enter limb bud early - because without innervation, development stops

Question 22

brachial plexus in relation to the nerves innervating

Answer 22

all muscles are compartmentalised, nerves grow into the common muscle masses
all anterior divisions regroup to form medial & lateral chords - innervating flexors (ventral)
all posterior divisions regroup to form posterior chord - innervating extensors (dorsal)

Question 23

what are dermatomes and myotomes?

Answer 23

derived from paraxial mesoderm
D: strip of skin supplied by a single spinal nerve
M: muscle / group of muscles supplied by single spinal nerve

Question 24

describe how nerves innervate dermatomes and myotomes

Answer 24

Nerve originate from somite segment (spinal root - C5-T1 upper)
as the embryo grows, morphological changes take the spinal nerve with it to innervate a strip of skin / group of muscles
there is no overlap between the segment of skin / muscle innervated by the nerves

Question 25

Limb defects

Answer 25

upper limbs (grows ahead 2 days) usually more affected than lower limbs
rare, usually hereditary
can be teratogen - induced malformity of embryo e.g. thalidomide

Question 26

What are some common limb defects?

Answer 26

Amelia: complete absence of a limb
Meromelia: partial absence of 1 or more limb structures
Phocomelia: deformity where limbs are attached close to trunk of body - seen when thalidomide given

Question 27

Common digit defects

Answer 27

syndactyly: fusion of digits, can be just CT or bones as well (lack of sculpting from apoptosis and AER maintained too long by ZPA)
polydactyly: extra digits, genetic recessive trait

Question 28

Limb development preaxial & postaxial

Answer 28

preaxial: thumb (radial) & big toe (tibial) (between C5 & C6)
postaxial: little finger (ulna) & little toe (fibula) (between C8 & T1)

Question 29

How does prenatal limb begin its development?

Answer 29

activation of mesenchyme (mesoderm CT) in somatic mesoderm (somatic (top) layer of lateral plate mesoderm)