Cell Differentiation and Limb Development

Question 1

what does limb development involve?

Answer 1

-cell differentiation
-pattern formation
-morphogenesis
-growth

Question 2

where do limbs develop from?

Answer 2

from small buds of undifferentiated mesoderm cells, which are covered by ectoderm

Question 3

when are limbs developed?

Answer 3

8 weeks

Question 4

when do limb buds first become visible?

Answer 4

end of week 4 (day 24)

Question 5

what do limb buds look like?

Answer 5

upper limb - appear first as ridges from ventrolateral body wall
lower limb - small bulges

Question 6

when does limb morphogenesis take place?

Answer 6

between weeks 4 and 8

Question 7

which limbs are often taking the lead in development?

Answer 7

upper limbs but lower limbs catch up by the end of the developmental period

Question 8

where is mesenchyme derived from?

Answer 8

dorsolateral mesoderm cells of the somites

Question 9

what are some types of mesenchymal connective tissue?

Answer 9

-matrix of collagen fibres
-hyaluronic acid
-glycoproteins

Question 10

are there nerves in the early limb buds?

Answer 10

no, none

Question 11

what is the 1st sign of limb musculature?

Answer 11

appearance of a condensation of mesenchyme near the limb buds

Question 12

what does the mesenchymal core of limb buds form?

Answer 12

somatic layer of the lateral plate mesoderm

Question 13

what covers the limb buds?

Answer 13

a layer of cuboidal ectoderm

Question 14

what happens when the ectoderm at the distal border thickens?

Answer 14

-Apical Ectoderm Ridge (AER)
-inductive relationship with mesoderm
-remains undifferentiated

Question 15

what do the cells furthest from the AER begin to differentiate into?

Answer 15

cartilage and muscle

Question 16

what happens without the AER?

Answer 16

-limbs fail to develop
-key signalling centre

Question 17

what does he position of the AER correspond to?

Answer 17

the border between dorsal and ventral ectoderm

Question 18

what are the T-box family transcription factors?

Answer 18

-TBX-5 expressed in upper limbs
-TBX-4 in the hind limbs

Question 19

what are some essential mesoderm and ectoderm interactions?

Answer 19

AER- promotes mitosis and prevents differentiation
-although AER is ectoderm and is acting on the mesoderm, its own existence is controlled by mesoderm

Question 20

what happens at week 6?

Answer 20

terminal portion of buds become flattened into hand plates and footplates
-seperated from the proximal segments by constriction
-a second constriction further divides proximal portion into two segments

Question 21

what are the 3 components that appear proximodistally?

Answer 21

stylopod - humerus and femur
zeugopod - radius/ulna and tibia/fibula
autopod - carpels, metacarpals, digits, tarsals/metatarsals

Question 22

what genes regulate the positioning of the limbs along the craniocaudal axis?

Answer 22

HOX genes
-expressed in overlapping patterns
-mis-expression alters limb position

Question 23

what is polydactyly?

Answer 23

extra digits, defect in mesoderm caused by mutation in Hox genes or Shh and Wnt
-inherited

Question 24

what are the stages in digit development?

Answer 24

-cell death in AER separates ridges into 5 parts, 5 digits grow out under influence of 5 ridge parts
-mesenchyme condenses to form cartilaginous digits
-by d56, digit separation complete

Question 25

when does limb rotation occur?

Answer 25

during week 7 and the upper and lower limbs rotate in opposite directions

Question 26

what happens during limb rotation?

Answer 26

limbs rotate 90degree
-upper limbs laterally, extensor muscles lie on the lateral and posterior side
-lower limbs medially, extensor muscles lie on the anterior surface

Question 27

where are limbs derived from?

Answer 27

the lateral mesoderm and overlying ectoderm

Question 28

what determines segments?

Answer 28

Hox genes

Question 29

how are axes fixed?

Answer 29

dorsoventral and sequence

Question 31

when can hyaline cartilage models be seen?

Answer 31

week 6
proximodistal sequence

Question 32

where are joints?

Answer 32

areas where condrogenesis is arrested
-cell proliferation, increased density, differentiation then cell deal, induced by WNT 14

Question 33

where do the centres of ossification form?

Answer 33

-diaphyses
-epiphyses
-present in all long bones by week 12
-growth plates of cartilage remain

Question 34

how can cartilage grow but bone cannot?

Answer 34

interstitial growth

Question 35

what can positional growth do?

Answer 35

increase width, intramembranous ossification from periosteum

Question 36

Give a timeline for Bone ossification

Answer 36

week 6 - cartilage models of bone form
week 8 - ossification begins
week 12 - primary centres of ossification in all long bones of limbs
birth - epiphyses still cartilaginous, secondary centres of ossification appear
puberty - growth plates close