Cell Differentiation and Limb Development Flashcards
what does limb development involve?
-cell differentiation
-pattern formation
-morphogenesis
-growth
where do limbs develop from?
from small buds of undifferentiated mesoderm cells, which are covered by ectoderm
when are limbs developed?
8 weeks
when do limb buds first become visible?
end of week 4 (day 24)
what do limb buds look like?
upper limb - appear first as ridges from ventrolateral body wall
lower limb - small bulges
when does limb morphogenesis take place?
between weeks 4 and 8
which limbs are often taking the lead in development?
upper limbs but lower limbs catch up by the end of the developmental period
where is mesenchyme derived from?
dorsolateral mesoderm cells of the somites
what are some types of mesenchymal connective tissue?
-matrix of collagen fibres
-hyaluronic acid
-glycoproteins
are there nerves in the early limb buds?
no, none
what is the 1st sign of limb musculature?
appearance of a condensation of mesenchyme near the limb buds
what does the mesenchymal core of limb buds form?
somatic layer of the lateral plate mesoderm
what covers the limb buds?
a layer of cuboidal ectoderm
what happens when the ectoderm at the distal border thickens?
-Apical Ectoderm Ridge (AER)
-inductive relationship with mesoderm
-remains undifferentiated
what do the cells furthest from the AER begin to differentiate into?
cartilage and muscle
what happens without the AER?
-limbs fail to develop
-key signalling centre
what does he position of the AER correspond to?
the border between dorsal and ventral ectoderm
what are the T-box family transcription factors?
-TBX-5 expressed in upper limbs
-TBX-4 in the hind limbs
what are some essential mesoderm and ectoderm interactions?
AER- promotes mitosis and prevents differentiation
-although AER is ectoderm and is acting on the mesoderm, its own existence is controlled by mesoderm
what happens at week 6?
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
what are the 3 components that appear proximodistally?
stylopod - humerus and femur
zeugopod - radius/ulna and tibia/fibula
autopod - carpels, metacarpals, digits, tarsals/metatarsals
what genes regulate the positioning of the limbs along the craniocaudal axis?
HOX genes
-expressed in overlapping patterns
-mis-expression alters limb position
what is polydactyly?
extra digits, defect in mesoderm caused by mutation in Hox genes or Shh and Wnt
-inherited
what are the stages in digit development?
-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
when does limb rotation occur?
during week 7 and the upper and lower limbs rotate in opposite directions
what happens during limb rotation?
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
where are limbs derived from?
the lateral mesoderm and overlying ectoderm
what determines segments?
Hox genes
how are axes fixed?
dorsoventral and sequence
when can hyaline cartilage models be seen?
week 6
proximodistal sequence
where are joints?
areas where condrogenesis is arrested
-cell proliferation, increased density, differentiation then cell deal, induced by WNT 14
where do the centres of ossification form?
-diaphyses
-epiphyses
-present in all long bones by week 12
-growth plates of cartilage remain
how can cartilage grow but bone cannot?
interstitial growth
what can positional growth do?
increase width, intramembranous ossification from periosteum
Give a timeline for Bone ossification
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
