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WEEK 24:

Embryology of limbs and clinical relevance:

QuestionAnswer
initial growth and patterning of the limbs occurs when during weeks 4-8
appearance of limb buds outpocketings at the end of week 4 (forelimb then hindlimb)
limb buds mesenchymal core derived from lateral plate mesoderm (bones and connective tissue) with an ectodermal outer layer
ectodermal layer development thickens distally and forms the apical ectodermal ridge (AER)
apical ectodermal ridge (AER) has inductive influence that regulates the undifferentiation and differentiation of cells
cells closer to the AER remain undifferentiated but rapidly proliferate
cells father away from AER begin to differentiate into cartilage and muscle
how do limbs grow proximo-distally
hand and footplates are formed as a result of what limb bud flattening (WEEK 6)
first circular constriction week 6- separates hand and foot plates from proximal segment
second circular constriction week 8- separates proximal segments into two
where does apoptosis occur at AER
further formation of digit formation depends on (3) continued outgrowth of AER (inductive influence), core of mesenchyme turning into cartilage, and death of intervening tissues between digits
digits fingers and toes (phalanges)
digits are initially interconnected by tissue which then regresses via apoptosis to produce separate digits
apoptosis of interdigital tissue is dependent on BMP signaling within the interdigital tissue under the influence of Shh from the zone of polarising activity (ZPA)
disruption of apoptosis of interdigital tissue can result in syndactyly (which often affects digits 3,4, and/or 5)
cartilage formation involves mesenchyme condenses and differentiates into chondrocytes where chondrocytes form the first hyaline cartilage models (week 6) needed for bone formation
what happens in the interzone chondrogenesis ceased and becomes joint
endochondral ossification occurs when starts by the end of week 8
endochondral ossification process mesenchyme condenses and differentiates into chondrocytes where chondrocytes form the first hyaline cartilage models and blood vessels invade the centre of diaphysis forming primary ossification centre (week 12) - bringing together osteoblast
secondary ossification centres are formed where and when epiphyses after birth (growth continues as chondrocytes proliferate)
how many growth plates in long bones 2
how many growth plates in smaller bones (phalanges) 1 - at the tip
primary ossification occurs at week 12 where they bring together osteoblast (bone forming cells) and shove proliferating chondrocytes to epiphyseal ends
body musculature derived from paraxial mesoderm (somites)
sclerotome develops into vertebral and rib bones
myotome develops into muscle
dermatome develops into dermal connective tissue
myotome can further be divided into primaxial (dorsomedial) and abaxial (ventrolateral) myotome
primaxial myotome (dorsomedial) somite-derived cells only - affected by signaling factors from the neural tube to generate muscle precursors with limited migratory potential
abaxial myotome (ventrolateral) respond to signals from adjacent lateral plate mesoderm to give rise to migratory population
limb bud elongation with migration of muscle cells includes splitting into flexors and extensors, back muscles innervated by dorsal ramus, and body wall and limb muscles innervated by ventral ramus
limb rotation involves dividing trunks and movement in both the upper and lower limb
trunk is divided into segments that receive innervation from spinal nerves
distal ends of limbs flatten into paddles- with the thumb and great toe most anterior and after flexure the elbow and knee lateral
limbs by week 7 undergo torsion in opposite directions, upper limb rotates 90* laterally while lower limb rotates 90* medially
limb rotation in the lower limb permanent pronation - which twists leg so that the foot faces downwards with great toe medial
dermatome area of skin supplied by single spinal nerve which is evenly spaced horizontally in thorax and abdomen but more complex in upper and lower limbs
regulation of limb bud identity establishment involves (3) paired like homeodomain transcription factor 1 (Pitx1), hindlimb-specific enhancer A/B (HLEA/B), and fibroblast growth factor 10 (Fgf10)
mechanism of regulation of limb bud identity establishment
sonic hedgehod (SHH) and noggin found in sclerotome
genes responsible for dermatome LOCATION ** PAX3 regulated by NT-3
genes responsible for DM muscle cells -> primaxial muscles MYF5 regulated by WNT
genes responsible for VL muscles -> abaxial muscles BMP4 and WNT regulates MyoD
PAX3 regulates NT-3
WNT regulates MYF5
BMP4 and WNT regulates MyoD
patterning, growth, and maturation of the limbs occurs along
proximo-distal growth and patterning S22
proximo-distal growth and patterning (S23)
antero-posterior patterning (A-P patterning)^^ established by zone of polarizing activity (ZPA) on the posterior side of limb (little finger side). SHH signaling from ZPA specifically signals formation of posterior elements
upregulation of ZPA signals results in additional posterior elements (polydactyly on hypothenar side of hand)
duplication of ZPA results in duplication of posterior elements (eg little fingers on both sides of thumb)
loss of ZPA results in loss of posterior elements
dorso-ventral patterning specifies dorsal surface (Extensors) vs ventral surface (flexors, palm/sole) of limbs
dorsal and ventral signaling factors
SLIDE 25
limb defects - amelia
limb defects - phocomelia
limb defects - amniotic bonds
limb defects - polydactyly
limb defects - syndactyly
limb defects - cleft foot
transverse limb deficiencies limb defects in which proximal structures are intact but structures distal to a transverse plane are partially or completely absent due to disruption of AER
osteogenesis imperfecta (brittle bones)
Created by: kablooey
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