page_title: Limb development
hierarchical_section_title: Limb development
context_page_description: Limb development in vertebrates is an area of active research in both developmental and evolutionary biology, with much of the latter work focused on the transition from fin to limb.
  Limb formation begins in the morphogenetic limb field, as mesenchymal cells from the lateral plate mesoderm proliferate to the point that they cause the ectoderm above to bulge out, forming a limb bud. Fibroblast growth factor induces the formation of an organizer at the end of the limb bud, called the apical ectodermal ridge, which guides further development and controls cell death. Programmed cell death is necessary to eliminate webbing between digits.
  The limb field is a region specified by expression of certain Hox genes, a subset of homeotic genes, and T-box transcription factors – Tbx5 for forelimb or wing development, and Tbx4 for leg or hindlimb development. Establishment of the forelimb field requires retinoic acid signaling in the developing trunk of the embryo from which the limb buds emerge.
context_section_description: Limb development in vertebrates is an area of active research in both developmental and evolutionary biology, with much of the latter work focused on the transition from fin to limb.
  Limb formation begins in the morphogenetic limb field, as mesenchymal cells from the lateral plate mesoderm proliferate to the point that they cause the ectoderm above to bulge out, forming a limb bud. Fibroblast growth factor (FGF) induces the formation of an organizer at the end of the limb bud, called the apical ectodermal ridge (AER), which guides further development and controls cell death. Programmed cell death is necessary to eliminate webbing between digits.
  The limb field is a region specified by expression of certain Hox genes, a subset of homeotic genes, and T-box transcription factors – Tbx5 for forelimb or wing development, and Tbx4 for leg or hindlimb development.  Establishment of the forelimb field (but not hindlimb field) requires retinoic acid signaling in the developing trunk of the embryo from which the limb buds emerge. Also, although excess retinoic acid can alter limb patterning by ectopically activating Shh or Meis1/Meis2 expression, genetic studies in mouse that eliminate retinoic acid synthesis have shown that RA is not required for limb patterning.
  The limb bud remains active throughout much of limb development as it stimulates the creation and positive feedback retention of two signaling regions: the AER and its subsequent creation of the zone of polarizing activity (ZPA) with the mesenchymal cells. In addition to the dorsal-ventral axis created by the ectodermal expression of competitive Wnt7a and BMP signals respectively, these AER and ZPA signaling centers are crucial to the proper formation of a limb that is correctly oriented with its corresponding axial polarity in the developing organism. Because these signaling systems reciprocally sustain each other’s activity, limb development is essentially autonomous after these signaling regions have been established.
caption: Illustration of a human embryo at six weeks gestational age
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