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.
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.
Hannah Research Institute, Ayr, Scotland, KA6 5HL, UK.
Gordon J
GJ
Allan
Augusta
A
Zannoni
Iain
I
McKinnell
William R
WR
Otto
Martin
M
Holzenberger
David J
DJ
Flint
Ketan
K
Patel
D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002642:Chick Embryo / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D053823:Hedgehog Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000302:isolation & purification; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics*; D014704:Veratrum Alkaloids / Q000494:pharmacology
D018076:DNA, Complementary; D053823:Hedgehog Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D015534:Trans-Activators; D014704:Veratrum Alkaloids; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; C000541:cyclopamine