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      Sonic hedgehog specifies flight feather positional information in avian wings

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          ABSTRACT

          Classical tissue recombination experiments performed in the chick embryo provide evidence that signals operating during early limb development specify the position and identity of feathers. Here, we show that Sonic hedgehog (Shh) signalling in the embryonic chick wing bud specifies positional information required for the formation of adult flight feathers in a defined spatial and temporal sequence that reflects their different identities. We also reveal that Shh signalling is interpreted into specific patterns of Sim1 and Zic transcription factor expression, providing evidence of a putative gene regulatory network operating in flight feather patterning. Our data suggest that flight feather specification involved the co-option of the pre-existing digit patterning mechanism and therefore uncovers an embryonic process that played a fundamental step in the evolution of avian flight.

          Abstract

          [Related article:] Highlighted Article: Embryonic Shh signalling integrates flight feather with digit specification in the chicken wing, providing insights into the evolution of avian flight.

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          Most cited references39

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          A series of normal stages in the development of the chick embryo

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            A series of normal stages in the development of the chick embryo.

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              Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.

              Basal cell carcinoma, medulloblastoma, rhabdomyosarcoma and other human tumours are associated with mutations that activate the proto-oncogene Smoothened (SMO) or that inactivate the tumour suppressor Patched (PTCH). Smoothened and Patched mediate the cellular response to the Hedgehog (Hh) secreted protein signal, and oncogenic mutations affecting these proteins cause excess activity of the Hh response pathway. Here we show that the plant-derived teratogen cyclopamine, which inhibits the Hh response, is a potential 'mechanism-based' therapeutic agent for treatment of these tumours. We show that cyclopamine or synthetic derivatives with improved potency block activation of the Hh response pathway and abnormal cell growth associated with both types of oncogenic mutation. Our results also indicate that cyclopamine may act by influencing the balance between active and inactive forms of Smoothened.
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                Author and article information

                Journal
                Development
                Development
                DEV
                develop
                Development (Cambridge, England)
                The Company of Biologists Ltd
                0950-1991
                1477-9129
                1 May 2020
                5 May 2020
                5 May 2020
                : 147
                : 9
                : dev188821
                Affiliations
                [1 ]Department of Biomedical Science, University of Sheffield, Western Bank , Sheffield S10 2TN, UK
                [2 ]Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (CSIC-Universidad de Cantabria - SODERCAN) , 39011 Santander, Spain
                [3 ]Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Cantabria , 39011 Santander, Spain
                Author notes
                [*]

                Present address: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.

                [‡]

                Present address: University of Florida, Gainesville, FL 32611, USA.

                [§]

                These authors contributed equally to this work

                Handling Editor: James Briscoe

                Author information
                http://orcid.org/0000-0002-1224-7671
                http://orcid.org/0000-0003-2189-4536
                Article
                DEV188821
                10.1242/dev.188821
                7225127
                32376617
                df97ecb9-d2c2-450f-a50e-4cf34c03e26f
                © 2020. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 27 January 2020
                : 24 March 2020
                Funding
                Funded by: Wellcome Trust, http://dx.doi.org/10.13039/100010269;
                Award ID: 202756/Z/16/Z
                Funded by: Ministerio de Ciencia, Innovación y Universidades;
                Award ID: BFU2017-88265-P
                Categories
                Research Article

                Developmental biology
                avian,chick,embryo,flight feather,positional information,shh
                Developmental biology
                avian, chick, embryo, flight feather, positional information, shh

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