Reference - Detail
|Author||Haramoto Y, Takahashi S, Oshima T, Onuma Y, Ito Y, Asashima M.|
|Title||Insulin-like factor regulates neural induction through an IGF1 receptor-independent mechanism.|
Insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) signalling is required for normal embryonic growth and development. Previous reports indicated that the IGF/IGF1R/MAPK pathway contributes to neural induction and the IGF/IGF1R/PI3K/Akt pathway to eye development. Here, we report the isolation of insulin3 encoding a novel insulin-like ligand involved in neural induction. Insulin3 has a similar structure to pro-insulin and mature IGF ligands, but cannot activate the IGF1 receptor. However, similar to IGFs, Insulin3 induced the gene expression of an anterior neural marker, otx2, and enlarged anterior head structures by inhibiting Wnt signalling. Insulin3 are predominantly localised to the endoplasmic reticulum when otx2 is induced by insulin3. Insulin3 reduced extracellular Wnts and cell surface localised Lrp6. These results suggest that Insulin3 is a novel cell-autonomous inhibitor of Wnt signalling. This study provides the first evidence that an insulin-like factor regulates neural induction through an IGF1R-independent mechanism.
|MeSH||Amino Acid Sequence Animals Blotting, Western Embryo, Nonmammalian / embryology Embryo, Nonmammalian / metabolism* Endoplasmic Reticulum / metabolism Gene Expression Regulation, Developmental In Situ Hybridization Low Density Lipoprotein Receptor-Related Protein-6 / genetics Low Density Lipoprotein Receptor-Related Protein-6 / metabolism Microscopy, Confocal Molecular Sequence Data Nervous System / embryology Nervous System / metabolism* Otx Transcription Factors / genetics Otx Transcription Factors / metabolism Receptor, IGF Type 1 / genetics* Receptor, IGF Type 1 / metabolism Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Somatomedins / genetics* Somatomedins / metabolism Wnt Signaling Pathway / genetics Xenopus / embryology Xenopus / metabolism Xenopus Proteins / genetics* Xenopus Proteins / metabolism Xenopus laevis / embryology Xenopus laevis / metabolism|