Overexpression of lunatic fringe does not affect epithelial cell differentiation in the developing mouse lung

• Published in: American journal of physiology. Lung cellular and molecular physiology 2005-04, Vol.288 (4), p.L672-L682
• Main Authors: van Tuyl, Minke, Groenman, Freek, Kuliszewski, Maciek, Ridsdale, Ross, Wang, Jinxia, Tibboel, Dick, Post, Martin
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors; Bronchi - metabolism; Calcitonin Gene-Related Peptide - metabolism; Cell Differentiation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epithelial Cells - cytology; Gene Expression Regulation, Developmental; Glycosyltransferases - genetics; Glycosyltransferases - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; In Situ Hybridization; Ligands; Lung - embryology; Membrane Proteins - metabolism; Mesoderm - metabolism; Mice; Mice, Transgenic; Neurosecretory Systems - metabolism; Receptors, Notch; Signal Transduction; Transcription Factor HES-1; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00247.2004

1 Lung Biology Research Program, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada; and 2 Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands Submitted 1 July 2004 ; accepted in final form 4 December 2004 The Notch/Notch-ligand pathway regulates cell fate decisions and patterning in various tissues. Several of its components are expressed in the developing lung, suggesting that this pathway is important for airway cellular patterning. Fringe proteins, which modulate Notch signaling, are crucial for defining morphogenic borders in several organs. Their role in controlling cellular differentiation along anterior-posterior axis of the airways is unknown. Herein, we report the temporal-spatial expression patterns of Lunatic fringe (Lfng) and Notch-regulated basic helix-loop-helix factors, Hes1 and Mash-1, during murine lung development. Lfng was only expressed during early development in epithelial cells lining the larger airways. Those epithelial cells also expressed Hes1 , but at later gestation Hes1 expression was confined to epithelium lining the terminal bronchioles. Mash-1 displayed a very characteristic expression pattern. It followed neural crest migration in the early lung, whereas at later stages Mash-1 was expressed in lung neuroendocrine cells. To clarify whether Lfng influences airway cell differentiation, Lfng was overexpressed in distal epithelial cells of the developing mouse lung. Overexpression of Lfng did not affect spatial or temporal expression of Hes1 and Mash-1 . Neuroendocrine CGRP and protein gene product 9.5 expression was not altered by Lfng overexpression. Expression of proximal ciliated ( -tubulin IV), nonciliated ( CCSP ), and distal epithelial cell ( SP-C , T1 ) markers also was not influenced by Lfng excess. Overexpression of Lfng had no effect on mesenchymal cell marker ( -sma, vWF, PECAM-1) expression. Collectively, the data suggest that Lunatic fringe does not play a significant role in determining cell fate in fetal airway epithelium. Notch signaling pathway; lung development; epithelial differentiation Address for reprint requests and other correspondence: M. Post, Prog. in Lung Biology Research, Hospital for Sick Children Research Inst., 555 Univ. Ave., Toronto, Ontario M5G1X8, Canada (E-mail: martin.post{at}sickkids.ca )