HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 43, 29532-29544, October 24, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/43/29532    most recent M801565200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsao, P.-N. Articles by Cardoso, W. V. Search for Related Content PubMed PubMed Citation Articles by Tsao, P.-N. Articles by Cardoso, W. V. Social Bookmarking                      What's this?

-Secretase Activation of Notch Signaling Regulates the Balance of Proximal and Distal Fates in Progenitor Cells of the Developing Lung^*

Po-Nien Tsao, Felicia Chen, Konstantin I. Izvolsky, Janice Walker^¶, Maria A. Kukuruzinska^||, Jining Lu, and Wellington V. Cardoso¹

From the Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, the ^||Department of Cell and Molecular Biology, Boston University School of Dental Medicine, Boston, Massachusetts 02118, the Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, and the ^¶Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Little is known about the mechanisms by which the lung epithelial progenitors are initially patterned and how proximal-distal boundaries are established and maintained when the lung primordium forms and starts to branch. Here we identified a number of Notch pathway components in respiratory progenitors of the early lung, and we investigated the role of Notch in lung pattern formation. By preventing -secretase cleavage of Notch receptors, we have disrupted global Notch signaling in the foregut and in the lung during the initial stages of murine lung morphogenesis. We demonstrate that Notch signaling is not necessary for lung bud initiation; however, Notch is required to maintain a balance of proximal-distal cell fates at these early stages. Disruption of Notch signaling dramatically expands the population of distal progenitors, altering morphogenetic boundaries and preventing formation of proximal structures. Our data suggest a novel mechanism in which Notch and fibroblast growth factor signaling interact to control the proximal-distal pattern of forming airways in the mammalian lung.

Received for publication, February 27, 2008 , and in revised form, July 17, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health, NHLBI, Grant PO1 HL47049 (to W. V. C.) and NIH/EE Grant 014798 (to J. W. and M. A. K.). This work was also supported by National Health Research Institutes-Taiwan Physician Scientist Award PS9402 (to P. N. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

¹ To whom correspondence should be addressed: Pulmonary Center, Boston University School of Medicine, 715 Albany St., R-304, Boston, MA 02118. Tel.: 617-638-6198; Fax: 617-536-8093; E-mail: wcardoso{at}bu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P.-N. Tsao, M. Vasconcelos, K. I. Izvolsky, J. Qian, J. Lu, and W. V. Cardoso Notch signaling controls the balance of ciliated and secretory cell fates in developing airways Development, July 1, 2009; 136(13): 2297 - 2307. [Abstract] [Full Text] [PDF]

				J. S. Guseh, S. A. Bores, B. Z. Stanger, Q. Zhou, W. J. Anderson, D. A. Melton, and J. Rajagopal Notch signaling promotes airway mucous metaplasia and inhibits alveolar development Development, May 15, 2009; 136(10): 1751 - 1759. [Abstract] [Full Text] [PDF]