Cyclopamine causes a homeotic frameshift of digital identity in the chicken wing


Meeting Abstract

34.5  Friday, Jan. 4  Cyclopamine causes a homeotic frameshift of digital identity in the chicken wing VARGAS, AO*; WAGNER, GP; Yale University; Yale University alexander.vargas@yale.edu

The identity of the digits in the bird wing has long been controversial. Comparative morphology indicates the digits to be 1, 2 and 3, but they develop from the embryological position of digits 2, 3 and 4. The Primary Axis (PA) is used to identify the positional homology of digits. The PA is the first digit to produce cartilage, is in line with the ulna and develops into digit 4 in pentadactyl amniotes. The frame shift hypothesis suggests that a hometic frame shift occurred in the lineage leading to birds, such that the PA in the wing develops into digit 3, rather than digit 4. Here we report that it is possible to experimentally obtain a homeotic frame shift. We used cyclopamine to down regulate Shh signaling in chicken wing buds at stage 21 (3.5 days). Cartilage staining of treated wings was observed at day 10 (n= 93), about 50% of the treated limbs have only two digits (46/93). Morphologically, there is no question that the two remaining digits are digits 1 and 2. Embryos at day 6 (stage 30) normally show cartilage condensations of all digits. Wings treated with cyclopamine only digits 1 and 2 can be identified (8/36). In these bi-dactyl limbs digit 2 is spatially in line with the ulna, like the PA. At an earlier stage (5.5 days, stage 27), treated and untreated limbs are indistinguishable, presenting a PA extending from the ulna (n=40). This implies digits 1 and 2 develop from embryological positions 3 and 4. Hoxd12 expression in day 6 bidactyl embryos (n=11) is absent only in digit 1, as expected. Our data suggests that down regulation of Shh signaling is sufficient to cause a homeotic frame shift and may have also accompanied the loss of digit 4 in the early theropod ancestors of birds.

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