Upper limb specification largely occurs during weeks four to six of embryogenesis. The majority of upper limb anomalies are produced at this stage of development. The limb bud develops from the migration of undfferentiated lateral plate somatic mesoderm into the overlying ectoderm in the region of the eighth to tenth somites along the lateral margin of the embryo. This region forms a 'morphogenetic field', that is a volume of cells which undergo similar forms of development as they lie within the same set of boundaries. Within the morphogenetic field of the limb bud, Hox gene expression makes cells competent to respond to the influence of different morphogen signals. The ectoderm thickens at this site to form the apical ectodermal ridge (AER). The AER acts as one of the signalling centers for further limb development.
Further development is orchestrated by a highly complex and stereotyped sequence of morphogen proteins that are part of separate signalling pathways. With some interplay of influence, discrete systems govern patterning of different anatomical axes:
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