Development of limbs and common congenital anomalies
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Limbs develop from limb buds that appear on the body wall, differentiate proximodistally, rotate, and ossify; disruption produces characteristic congenital limb anomalies.
Limb Bud Formation and Differentiation
Limb skeletal components develop from lateral plate mesoderm.
Mesoderm migrates into the limb bud and condenses along its central axis in a proximodistal sequence regulated by Hox genes, which also position the limbs along the craniocaudal body axis.
Limb buds appear as outpouchings from the ventrolateral body wall, end of the 4th week; forelimb first.
Hindlimb buds appear 1 to 2 days after forelimb buds.
Ectoderm at the bud tip thickens into the apical ectodermal ridge (AER).