Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo.
The insulin-like growth factor (IGF) signalling pathway has been highly conserved in animal evolution and, in mammals and Xenopus, plays a key role in embryonic growth and development, with the IGF-1 receptor (IGF-1R) being a crucial regulator of the signalling cascade. Here we report the first functional role for the IGF pathway in zebrafish. Expression of mRNA coding for a dominant negative IGF-1R resulted in embryos that were small in size compared to controls and had disrupted head and CNS development. At its most extreme, this phenotype was characterized by a complete loss of head and eye structures, an absence of notochord and the presence of abnormal somites. In contrast, up-regulation of IGF signalling following injection of IGF-1 mRNA, resulted in a greatly expanded development of anterior structures at the expense of trunk and tail. IGF-1R knockdown caused a significant decrease in the expression of Otx2, Rx3, FGF8, Pax6.2 and Ntl, while excess IGF signalling expanded Otx2 expression in presumptive forebrain tissue and widened the Ntl expression domain in the developing notochord. The observation that IGF-1R knockdown reduced expression of two key organizer genes (chordin and goosecoid) suggests that IGF signalling plays a role in regulating zebrafish organizer activity. This is supported by the expression of IGF-1, IGF-2 and IGF-1R in shield-stage zebrafish embryos and the demonstration that IGF signalling influences expression of BMP2b, a gene that plays an important role in zebrafish pattern formation. Our data is consistent with a common pathway for integration of IGF, FGF8 and anti-BMPs in early vertebrate development.
Eivers
Edward
E
Department of Biochemistry, National University of Ireland, Galway, Ireland.
McCarthy
Karena
K
Glynn
Catherine
C
Nolan
Catherine M
CM
Byrnes
Lucy
L
D000818:Animals; D015153:Blotting, Western; D019521:Body Patterning; D002490:Central Nervous System / Q000378:metabolism; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006023:Glycoproteins / Q000378:metabolism; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D009672:Notochord / Q000378:metabolism; D051857:Otx Transcription Factors; D010641:Phenotype; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D015027:Zebrafish; D029961:Zebrafish Proteins
D006023:Glycoproteins; D051956:Goosecoid Protein; C497993:Gsc protein, mouse; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D013002:Somatomedins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C497995:gsc protein, zebrafish; C497662:otx2b protein, zebrafish; D007334:Insulin-Like Growth Factor I; C054234:chordin; D017526:Receptor, IGF Type 1