cell differentiation and limb development Flashcards
mesenchyme
- type of connective tissue that is found during development of the embryo
- arises from the mesoderm
- contains loosely packed cells which are non specialised
- mesenchymal cells are highly migratory
apical ectodermal ridge, AER
- ectoderm in origin
- acting on the mesoderm in an inductive relationship, but its own existence is controlled by the mesoderm.
limb mesoderm
- if removed/disruption in signalling, limbs fail to form
- transplant mesoderm to the different area of embryo, an extra limb will form at site
- if remove ectoderm over limb, new ectoderm will grow and cover defect, limbs forms
- if ectoderm is moved to new site, no limb will form
time clock for limb specification
- mesoderm is also thought to set the time clock for limb specification
- cells moving from this region are fixed in their development potential, those leaving earlier have different cpabilities than those leaving later
- these cells have received specific positional info that will determine the type of tissue they will become
appositional growth
increase in girth/width - Chondroblasts deposit collagen matrix on cartilage beneath the periosteum which initiates growth of the bone width-wis
interstitial growth
increase in length, this is achieved by the growth plate up until puberty during the growth period
endochondral ossification
Cartilage model is laid down as a precursor to bone - mainly long bones.
intramembranous ossification
– Cartilage not involved, this is achieved by condsensation of mesenchyme which is converted straight to bone. See this in flat bones in the body.
congenital issues
conditions affecting the upper limb are more common than those affecting the lower limb
- congenital issues affecting the limbs can often be associated with craniofacial, cardiac and or genito-urinary complications
achondroplasia
- disorder of bone growth that affects endochondral ossification via cartilage, particularly affecting the long bones of the legs and arms
- autosomal dominant condition, most resulting from sporadic mutation. caused by a mutation in fibroblast growth factor receptor 3
- normally diagnosed during ultrasound at 20 weeks of gestation
- FGFR3 normally down regulates cartilage and bone growth. inhibits cell proliferation and differentiation.
limb development
Limbs develop from small buds of undifferentiated mesoderm cells, which are covered by ectoderm
At the end of week 4, limb buds first become visible (d24)
Upper limb buds appear first as ridges from ventrolateral body wall
Lower limb as small bulges
Limb morphogenesis takes. place between weeks 4 and 8
Lower limb lags slightly behind, but catches up by end of developmental period
limb musculature
1st sign is appearance of a condensation of mesenchyme near the limb buds
Mesenchyme is derived from the dorsolateral mesoderm cells of the somites
Mesenchymal connective tissue
Matrix of collagen fibres
Hyaluronic acid
Glycoproteins
No nerves in the early limb bud
limb development- limb buds
Limb buds consist of a mesenchymal core
From somatic layer of lateral plate mesoderm
Covered by layer of cuboidal ectoderm
Ectoderm at the distal border thickens
Apical Ectodermal Ridge (AER)
Inductive relationship with mesoderm
Remains undifferentiated
limb development- AER
As the limb grows, the cells furthest from the AER begin to differentiate into cartilage and muscle
Without the AER
limb fails to develop
key signalling centre
Position of AER corresponds to border between dorsal and ventral ectoderm
mesoderm and ectoderm interactions
Essential
AER – promotes mitosis
- prevents differentiation
Although AER is ectoderm and is acting on the mesoderm, its own existence is controlled by mesoderm
steps in limb development
At 6 week, terminal portion of buds become flattened
Handplates
Footplates
Separated from the proximal segments by constriction
A second constriction further divides proximal portion into two segments
steps in limd development- cell death in AER
Cell death in the 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 is complete
steps in limb development- three components
Development of the limb proceeds PROXIMODISTALLY into three components
Stylopod – humerus and femur
Zeugopod – radius/ulna and tibia/fibula
Autopod – carpels, metacarpals, digits, tarsals/metatarsals
control of limb development
Positioning of the limbs along the craniocaudal axis is regulated by HOX genes
Expressed in overlapping patterns
Mis-expression alters limb position
polydactyly
Extra digits - defect in mesoderm caused by mutation in Hox genes, Shh or Wnt
Inherited in humans as a genetic recessive trait
limb rotation
Development of the upper and lower limb is similar, apart from timing – Lower 1-2 days behind
During week 7 limb rotation occurs and the upper and lower limbs rotate in opposite directions
limb rotation- lateral and medial
Upper limb rotates 90o laterally
Extensor muscles lie on the lateral and posterior side (thumb laterally, elbows pointing back)
Lower limb rotates 90o medially
Extensor muscles lie on anterior surface (big toe lies medially, knees face forward)
stages of limb bone development
As the external shape is being established, mesenchyme in the limb buds becomes condensed
Cells differentiate into chondrocytes
Expression of BMPs drive this
At week 6, hyaline cartilage models can be seen
Proximodistal sequence
Areas where chondrogenesis is arrested makes joints
Cell proliferation, increased density, differentiation then cell death – induced by WNT 14
limb bone development- centre of ossification
Centres of ossification form
Diaphyses
Epiphyses
Primary centres of ossification are present in all long bones by week 12
Growth plates of cartilage remain
growth of long bone
During childhood, bones must grow
In length
In width
Cartilage is capable of interstitial growth - bone is not
Appositional growth can increase width
Intramembranous ossification from periosteum
Need interstitial growth, therefore must keep growth plate of cartilage during growth period
week 6-12 summary
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
