Flashcards in Development of the Limbs Deck (51):
With reference to a limb, what is meant by pentadactyl?
When do primary ossification and secondary ossification occur?
Primary takes place pre-birth (i.e. @ embryonic stage)
Secondary ossification centres arise @ birth
List the stages of endochondrial ossification from mesenchyme to mature bone.
Mesenchyme --condensation--> cartilage surrounded by mesenchyme ---> primary ossification centre (@ 12 weeks), proliferating chondroblasts, osteoblasts & angiogenesis ---> secondary ossification centres and growth plates develop
How can radiologists determine the skeletal age of a patient?
Examining epiphyseal plate development
What is meant by intramembranous ossification?
The formation of bone in fibrous connective tissue
What is fibrous connective tissue formed from?
Condensed mesenchyme cells
When does intramembranous ossification occur?
During the formation of flat bones
The limbs undergo rotation during embryonic development. After how long does this happen and to what degree, in which direction do the limbs rotate?
FORElimbs rotate 90 degrees LATERALLY
HIND limbs rotate 90 degrees MEDIALLY
What does this rotation result in with regard to muscle compartments in the limbs?
Flexor compartment anterior in upper limb and posterior in lower limb
When do upper limb buds appear?
When do lower limb buds appear?
Between which somites do upper limb buds appear?
C5 - T1
Between which somites do lower limb buds appear?
L1 - S2
How long is it before all major compartments of the limbs are present?
By week 8
What is the function of HOX genes?
To control limb development
Where are HOX genes expressed?
Along the long axis of the embryo - from head to tail; each number HOX gene follows the body plan, i.e. 1 is most superior, 13 is most inferior
Which class of proteins do HOX genes belong to?
What is the function of transcription factors?
Bind to DNA and regulate the transcription of other genes
During embryonic development, what two things do HOX genes determine?
Position of the limbs
Which three axes is limb growth regulated along?
What is another name for the antero-posterior axis?
Standard meanings of anterior & posterior and dorsal & ventral are very similar. How does this vary in embryology?
Anterior = lateral
Posterior = medial
Ventral = anterior
Dorsal = posterior
What is proximo-distal development controlled by?
APICAL ECTODERMAL RIDGE (AER)
Where is the core of mesenchyme derived from?
Lateral plate mesoderm
Where is the AER located and what forms it?
Ectoderm thickened at the apex of developing limb ---> AER
The AER induces the underlying tissue to remain as a population of undifferentiated, rapidly proliferating cells. What is this area known as?
The PROGRESS ZONE
How does cell differentiation come about if AER disallows it then?
As the AER progresses, it leaves cells behind; the further the AER travels away from these cells, the less of an influence it has over them , leaving them free to differentiate into cartilage and muscle
What controls the position of the limb on the long axis of the body?
What initiates growth of the fore-limbs
TBX5 & FGF-10
How is the progress zone maintained and development of the proximo-distal axis furthered?
FGF4 & FGF8
What are FGF4 & FGF8 examples of?
What controls the anterior-posterior/cranio-caudal axis?
ZONE OF POLARISING ACTIVITY (ZPA)
Where is the ZPA located?
Near the posterior border of the limb
With respect to the hand, what does the ZPA ensure?
That the thumb goes on the anterior (cranial) side of the limb bud
What initiates growth of the hind limbs?
What protein specifically does the ZPA express?
Sonic hedgehog protein
In which direction does the ZPA move?
Distally, with the AER
If another ZPA were to be added to the limb bud, what would be the effect on the limb?
Mirror image duplicates of the digits would arise
The doors-ventral axis determination involves EN1, LMX1, BMPs,& WNT7. Describe the sequence of events that occur resulting in certain cells being specified as being dorsal.
BMPs in ventral ectoderm induce/activate EN1
EN1 represses WNT7, restricting its expression to dorsal limb ectoderm
WNT7 induces/activates LMX1 which specifies cells to be dorsal
How is it that the upper and lower limbs are developed differently and patterns for proximal, middle and distal sections of limbs are defined?
Variations in the combinations of HOX genes ensure these differences
How is it that humans don't have webbed hands or webbed feet?
Programmed cell death is brought about between digits
Complete absence of the limbs
Partial absence of the limbs
Absence of long bones
Segments are abnormally short
Briefly summarise the Thalidomide tragedy.
Between 1957 & 1962, thalidomide was prescribed as a sleeping pill - increase in limb abnormalities was reported in newborns
Which element of limb development did thalidomide target?
The Progress Zone
What is Holt Oram Syndrome?
TBX5 mutation ---> failure of upper limb bud development
Also associated with heart defects
Fused digits - failure of apoptosis