Role for FGFR2IIIb-mediated signals in controlling pancreatic endocrine progenitor cell proliferation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Elghazi, L; Cras-Meneur, C; Czernichow, P; Scharfmann, R
Abstract
Pancreatic development is a classic example of epithelium-mesenchyme interaction. During embryonic life, signals from the mesenchyme control the proliferation of precursor cells within the pancreatic epithelium and their differentiation into endocrine or acinar cells. It has been shown that signals from the mesenchyme activate epithelial cell proliferation but repress development of the pancreatic epithelium into endocrine cells. Here, experiments with specific inhibitors established that mesenchymal effects on epithelial cell development depended on the mitogen-activated protein kinase pathway. Then we demonstrated that these effects of the mesenchyme were mimicked by fibroblast growth factor 7 (FGF7), a specific ligand of FGFR2IIIb, which is a tyrosine kinase receptor of the FGF-receptor family. When pancreatic epithelium expressing FGFR2IIIb was grown with FGF7, epithelial cell growth occurred in a concentration-dependent manner, whereas endocrine tissue development was repressed. The epithelial cells that proliferated in response to FGF7 were endocrine pancreatic precursor cells, as shown by their differentiation en masse into endocrine cells on FGF7 removal. Thus, efficient propagation of pancreatic progenitor cells can be achieved in vitro by exposure to FGF7, which does not affect their ability to differentiate en masse into endocrine cells on FGF7 removal.
Biomaterial mediated epithelial-mesenchymal interaction of salivary tissue under serum free condition
BIOMATERIALS
Authors: Yang, Tsung-Lin; Hsiao, Ya-Chuan; Lin, Sung-Jan; Lee, Hao-Wei; Lou, Pei-Jen; Ko, Jenq-Yuh; Young, Tai-Horng
Abstract
Many organs develop from epithelial-mesenchymal interactions such that in order to regenerate these organs, it might be a preferable strategy to recapitulate this process. However, in the current culture system designed for tissue interaction, the supplement of serum is required. The aim of this study is to explore the possibility of reproducing epithelial-mesenchymal interaction and ensuing morphogenesis in a serum-free condition. In accordance with the previous studies, by using a standard model of murine fetal submandibular gland (SMG), the tissue interaction and the morphogenesis were largely dependent on serum. Nonetheless, when tissue recombinants were cultivated on polyvinylidene fluoride (PVDF), but not on other biomaterials, the serum-deprived effect could be rescued. On PVDF, SMG tissue recombinant was able to increase epithelial size, de novo synthesize basement membrane, and develop new branches without serum. Although the gene expression levels of selected morphogens were not significantly altered, the precise localization of morphogenetic-decisive extracellular matrix such as type III collagen and the superior adsorbing capacity of essential diffusible factors like fibroblast growth factor 7 (FGF7) might account for PVDF effect. Accordingly, the result demonstrates that it is possible to establish a serum-free system that is competent in facilitating epithelial-mesenchymal interaction of salivary tissue. With PVDF, the crosstalk between SMG epithelia and mesenchyme could be sustained without serum. (C) 2009 Elsevier Ltd. All rights reserved.