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Major components of the insulin-like growth factor axis are expressed early in chicken embryogenesis, with IGF binding protein (IGFBP)-5 expression subject to regulation by Sonic Hedgehog

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Abstract

Using whole-mount in situ hybridisation techniques, we have examined the expression of major components of the insulin-like growth factor (IGF) axis in early development of the chicken embryo, including both IGF-I and -II, the type 1 IGF receptor (IGFR), and two of the IGF binding proteins, (IGFBP)-2 and -5. We report that these genes fall into two distinct groups with respect to expression pattern, with IGFBP-2 displaying broad overlap of mRNA expression with IGFR and IGF-I during early development, whereas the expression profile of IGFBP-5 most closely resembled that of IGF-II. Comparison between different stages revealed IGFBP-2 mRNA was detected as early as stage 3, whereas IGFBP-5 was first seen at stage 4. In addition, we detected expression domains of IGFBP-5, and to a lesser extent IGFBP-2, which did not overlap with either IGFR or IGF expression patterns. This could indicate IGF independent actions of the IGFBPs during early embryonic development. A striking observation concerning the expression profiles of both IGF-II and IGFBP-5 at early stages of chick embryogenesis is that both these genes are expressed asymmetrically in a pattern similar to that of Sonic Hedgehog (Shh). Furthermore, using cyclopamine, we have demonstrated that IGFBP-5 expression in the early embryo is regulated by Shh. Taken together, these results describe an important role for the IGF system in the very early stages of the developing chicken embryo, and imply that IGFBP-2 and -5 are fundamental developmental factors, with the latter involved in Shh signalling pathways.

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Acknowledgements

This work was supported by the Scottish Executive Rural Affairs Department. K.P. and I.M. wish to acknowledge generous funding from The Wellcome Trust (Grant 061425). We would like to acknowledge the assistance of Elaine Shervill and Petr Valasek in the preparation of tissue sections and photography.

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Authors and Affiliations

  1. Hannah Research Institute, Ayr, Scotland, KA6 5HL, UK

    Gordon J. Allan & David J. Flint

  2. Dipartimento di Morfofisiologia Veterinaria e Produzioni Animali, Via Tolara di Sopra 50, Ozzano Emilia, 40064, Bologna , Italy

    Augusta Zannoni

  3. Veterinary Basic Sciences, Royal Veterinary College, Royal College Street , London, NW1 OTU, UK

    Iain McKinnell & Ketan Patel

  4. Histopathology Unit, Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    William R. Otto

  5. Institut National de la Santé et de la Recherche Médicale U515, Hôpital Saint-Antoine, 75571, Paris 12, France

    Martin Holzenberger

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  1. Gordon J. Allan
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Correspondence to Ketan Patel.

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Allan, G.J., Zannoni, A., McKinnell, I. et al. Major components of the insulin-like growth factor axis are expressed early in chicken embryogenesis, with IGF binding protein (IGFBP)-5 expression subject to regulation by Sonic Hedgehog. Anat Embryol 207, 73–84 (2003). https://doi.org/10.1007/s00429-003-0321-x

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