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

J. Biol. Chem., Vol. 281, Issue 51, 39620-39629, December 22, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/51/39620    most recent M607886200v1 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 Böse, K. Articles by Smyth, N. Search for Related Content PubMed PubMed Citation Articles by Böse, K. Articles by Smyth, N. Social Bookmarking                      What's this?

Loss of Nidogen-1 and -2 Results in Syndactyly and Changes in Limb Development^*

Kerstin Böse, Roswitha Nischt^¶, Anton Page^||, Bernhard L. Bader^**, Mats Paulsson, and Neil Smyth¹

From the Center for Biochemistry and Center for Molecular Medicine, Medical Faculty, University of Cologne, D-50924 Cologne, Germany, the Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada, the ^¶Department of Dermatology, University of Cologne, D-50924 Cologne, Germany, ^||Biological Imaging Services, University of Southampton, Southampton SO16 6YD, United Kingdom, the ^**Department of Nutritional Medicine, Technical University Munich, D-85350 Freising, Germany, and the School of Biological Sciences, University of Southampton, Southampton SO16 7PX, United Kingdom

Nidogens are two ubiquitous basement membrane proteins produced mainly by mesenchymal cells. Nidogen-mediated interactions, in particular with laminin, collagen IV, and perlecan have been considered important in the formation and maintenance of the basement membrane. However, whereas mice lacking both nidogen isoforms or carrying mutations in the high affinity nidogen-binding site upon the laminin 1 chain have specific basement membrane defects in certain organs, particularly in the lung, characterization of these mice has also shown that basement membrane formation per se does not need nidogens or the laminin-nidogen interaction. Limb development requires the complex interplay of numerous growth factors whose expression is dependent upon the apical ectodermal ridge. Here, we show that lack of nidogen-1 and -2 results in a specific and time-limited failure in the ectodermal basement membrane of the limb bud. The absence of this basement membrane leads to aberrant apical ectodermal ridge formation. It also causes altered distribution of growth factors, such as fibroblast growth factors and leads to a fully penetrant soft tissue syndactyly caused by the dysregulation of interdigital apoptosis. Further, in certain animals more severe changes in bone formation occur, providing evidence for the interplay between growth factors and the extracellular matrix.

Received for publication, August 17, 2006 , and in revised form, September 29, 2006.

^* This work was supported by the Center for Molecular Medicine Cologne and by Deutsche Forschungsgemeinschaft Grant SFB-589. 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.

¹ To whom correspondence should be addressed: School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, United Kingdom. Tel.: 44-23-8059-7382; Fax: 44-23-8059-4459; E-mail: N.R.Smyth{at}soton.ac.uk.

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

This article has been cited by other articles:

				V. S. LeBleu, B. MacDonald, and R. Kalluri Structure and Function of Basement Membranes Experimental Biology and Medicine, October 1, 2007; 232(9): 1121 - 1129. [Abstract] [Full Text] [PDF]