Patterns & Phenotypes
Role for notch signaling in salivary acinar cell growth and differentiation
Version of Record online: 22 FEB 2009
Copyright © 2009 Wiley-Liss, Inc.
Volume 238, Issue 3, pages 724–731, March 2009
How to Cite
Dang, H., Lin, A. L., Zhang, B., Zhang, H.-M., Katz, M. S. and Yeh, C.-K. (2009), Role for notch signaling in salivary acinar cell growth and differentiation. Dev. Dyn., 238: 724–731. doi: 10.1002/dvdy.21875
- Issue online: 22 FEB 2009
- Version of Record online: 22 FEB 2009
- Manuscript Accepted: 26 DEC 2008
- National Institute of Dental and Craniofacial Research. Grant Number: R21 DE15381
- National Heart Lung and Blood Institute. Grant Number: R01 HL75011
- Department of Veterans Affairs
- salivary gland;
- epithelial cell differentiation;
The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of γ-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by γ-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation. Developmental Dynamics 238:724–731, 2009. © 2009 Wiley-Liss, Inc.