text: Essentially, Hox genes contribute to the specification of three main components of limb development, including the stylopod, zeugopod and autopod.  Certain mutations in Hox genes can potentially lead to the proximal and/or distal losses along with different abnormalities. Three different models have been created for outlining the patterning of these regions.  The Zone of polarizing activity (ZPA) in the limb bud has pattern-organizing activity through the utilization of a morphogen gradient of a protein called Sonic hedgehog (Shh). Sonic hedgehog is turned on in the posterior region via the early expression of HoxD genes, along with the expression of Hoxb8. Shh is maintained in the posterior through a feedback loop between the ZPA and the AER. Shh cleaves the Ci/Gli3 transcriptional repressor complex to convert the transcription factor Gli3 to an activator, which activates the transcription of HoxD genes along the anterior/posterior axis. It is evident that different Hox genes are critical for proper limb development in different amphibians.
  Researchers conducted a study targeting the Hox-9 to Hox-13 genes in different species of frogs and other amphibians. Similar to an ancient tetrapod group with assorted limb types, it is important to note that amphibians are required for the understanding of the origin and diversification of limbs in different land vertebrates. A PCR (Polymerase Chain Reaction) study was conducted in two species of each amphibian order to identify Hox-9 to Hox-13. Fifteen distinct posterior Hox genes and one retro-pseudogene were identified, and the former confirm the existence of four Hox clusters in each amphibian order. Certain genes expected to occur in all tetrapods, based on the posterior Hox complement of mammals, fishes and coelacanth, were not recovered. HoxD-12 is absent in frogs and possibly other amphibians. By definition, the autopodium is distal segment of a limb, comprising the hand or foot. Considering Hox-12’s function in autopodium development, the loss of this gene may be related to the absence of the fifth finger in frogs and salamanders.