{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:36:52Z","timestamp":1788345412166,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,8,28]],"date-time":"2013-08-28T00:00:00Z","timestamp":1377648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University of Otago Research Grant"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The vertebrate limb is one of the most intensively studied organs in the field of developmental biology. Limb development in tetrapod vertebrates is highly conserved and dependent on the interaction of several important molecular pathways. The bone morphogenetic protein (<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>) signaling cascade is one of these pathways and has been shown to be crucial for several aspects of limb development. Here, we have used a <jats:italic><jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>enopus laevis<\/jats:italic> transgenic line, in which expression of the inhibitor <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>oggin is under the control of the heat\u2010shock promoter <jats:italic>hsp70<\/jats:italic> to examine the effects of attenuation of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> signaling at different stages of limb development. Remarkably different phenotypes were produced at different stages, illustrating the varied roles of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> in development of the limb. Very early limb buds appeared to be refractory to the effects of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> attenuation, developing normally in most cases. Ectopic limbs were produced by overexpression of <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>oggin corresponding to a brief window of limb development at about stage 49\/50, as recently described by Christen et\u00a0al. (2012). Attenuation of <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> signaling in stage 51 or 52 tadpoles lead to a reduction in the number of digits formed, resulting in hypodactyly or ectrodactyly, as well as occasional defects in the more proximal tibia\u2010fibula. Finally, inhibition at stage 54 (paddle stage) led to the formation of dramatically shortened digits resulting from loss of distal phalanges. Transcriptome analysis has revealed the possibility that more <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>oggin\u2010sensitive members of the <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content> family could be involved in limb development than previously suspected. Our analysis demonstrates the usefulness of heat\u2010shock\u2010driven gene expression as an effective method for inhibiting a developmental pathway at different times during limb development.<\/jats:p>","DOI":"10.1111\/joa.12098","type":"journal-article","created":{"date-parts":[[2013,8,28]],"date-time":"2013-08-28T05:12:49Z","timestamp":1377666769000},"page":"474-488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Attenuation of bone morphogenetic protein signaling during amphibian limb development results in the generation of stage\u2010specific defects"],"prefix":"10.1111","volume":"223","author":[{"given":"Tamsin E. 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