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Loss of nidogen-1 and-2 results in syndactyly and changes in limb development

Bose, K., Nischt, R., Page, A., Bader, B.L., Paulsson, M. and Smyth, N. (2006) Loss of nidogen-1 and-2 results in syndactyly and changes in limb development The Journal of Biological Chemistry, 281, (51), pp. 39620-39629. (doi:10.1074/jbc.M607886200).

Record type: Article

Abstract

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.

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Published date: 1 December 2006

Identifiers

Local EPrints ID: 56619
URI: http://eprints.soton.ac.uk/id/eprint/56619
ISSN: 0021-9258
PURE UUID: 367f7ca8-32de-4344-ab30-ddf15d2ee84a

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Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:30

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Contributors

Author: K. Bose
Author: R. Nischt
Author: A. Page
Author: B.L. Bader
Author: M. Paulsson
Author: N. Smyth

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