title: Loss of nidogen-1 and -2 results in syndactyly and changes in limb development.
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 gamma1 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.
authors.affiliation: Center for Biochemistry and Center for Molecular Medicine, Medical Faculty, University of Cologne, D-50924 Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Böse
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
authors.forename: Anton
authors.initials: A
authors.lastname: Page
authors.forename: Bernhard L
authors.initials: BL
authors.lastname: Bader
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D004475:Ectoderm / Q000378:metabolism; D005091:Exons; D005121:Extremities / Q000196:embryology*; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011509:Proteoglycans / Q000378:metabolism; D013576:Syndactyly / Q000235:genetics* / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; C496457:Fgf8 protein, mouse; D008562:Membrane Glycoproteins; C114729:NID2 protein, human; D011509:Proteoglycans; C029967:nidogen; D051524:Fibroblast Growth Factor 8