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Limb Development

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Brock University
Daniel Glenday

Limb Development Timeline – buds appear at 26d – somites 8-12 lower buds at 28d – somites 24-29 complete at 56d Embryological Origins of limb components: skin = surface ectoderm melanocytes = NCC sensory neurons = NCC motor neurons = neural tube myotome (somites) = muscle somatic lateral plate mesoderm + ectoderm = limb buds (bones, tendons, ligaments, dermis) AER – apical ectodermal ridge AER divides limb bud into dorsal-ventral transplanted ectoderm can form new AER induced by mesenchyme **both need to be functioning for proper limb-bud development PROGRESS ZONE – actively dividing cells adjacent to AER Progress Zone mesenchyme here determines proximal/distal patterning “rejacketing experiments” – late mesenchyme + early cap  only distal elements form **age of mesenchyme determines proximal/distal fate** Limb Development LIMB POSITIONING along anterior/posterior body axis FGF-8 induces limb bud formation (which leads to AER FGF-8 formation) FGF-soaked beads can induce an entire ectopic limb - however, polarity is reversed (mirror-image limb forms) FGF-10 is initially expressed broadly throughout mesoderm FGF-10 localized FGF expression is necessary for limb bud formation localized FGF levels are also higher concentration Hox, Wnt genes likely candidates for positioning FGF-10 knockouts  no limbs mesoderm FGF-10 induces AER FGF-8 expression FGF-8: positive feedback to underlying mesenchyme (FGF-10 expression) FGF-8 in mesenchyme also induces SHH expression SHH for anterior/posterior limb patterning Limb Development LIMB BUD OUTGROWTH: PROXIMAL/DISTAL PATTERN prox/dist fate depends on how long mesenchyme is under influence of the AER (which is secreting FGF) BMP2 inhibits cell division in limb buds (antagonizes FGF)BMP-2 necessary for apoptotic signals in digit formation
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