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Publication : Sonic hedgehog signaling regulates the expression of insulin-like growth factor binding protein-6 during fetal prostate development.

First Author  Lipinski RJ Year  2005
Journal  Dev Dyn Volume  233
Issue  3 Pages  829-36
PubMed ID  15906375 Mgi Jnum  J:98927
Mgi Id  MGI:3580742 Doi  10.1002/dvdy.20414
Citation  Lipinski RJ, et al. (2005) Sonic hedgehog signaling regulates the expression of insulin-like growth factor binding protein-6 during fetal prostate development. Dev Dyn 233(3):829-36
abstractText  At the onset of ductal morphogenesis in the developing prostate, Shh expression condenses at evaginations of urogenital sinus epithelium and activates Gli transcription factors in the adjacent mesenchyme. Abrogation of Hedgehog signaling disrupts proper prostatic budding, ductal growth, and branching. We now show that Hedgehog signaling regulates the expression of insulin-like growth factor binding protein-6 (Igfbp-6) in the developing mouse prostate. Igfbp-6 is a secreted factor that specifically binds insulin-like growth factor-II (IGF-II), prevents its binding to the IGF-I receptor, and is thought to regulate the activity of IGF-II in growth and differentiation. Igfbp-6 is expressed in both the developing and adult prostate. In the urogenital sinus, Igfbp-6 mRNA colocalized with Ptc1 and Gli1 mRNA in the mesenchyme, while Igfbp-6 protein was found in both the mesenchymal and epithelial layers. Exogenous Shh peptide induced expression of Igfbp-6 in the developing prostate while the chemical inhibitor of Hedgehog signaling, cyclopamine, reduced its expression. These studies show that Igfbp-6 is an actual target of Shh signaling in the urogenital sinus and provide the first evidence for a linkage between the Hedgehog and IGF signaling pathways in prostate development.
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