1. ¹Department of Dermatology, University of Cologne, Cologne, Germany
2. ²German Cancer Research Center, Division A110 (A080), Heidelberg, Germany
3. ³School of Biological Science, University of Southampton, Southampton, UK

Correspondence: Dr Roswitha Nischt, Department of Dermatology, University of Cologne, Kerpener Strasse 62, Cologne 50937, Germany. E-mail: Roswitha.Nischt@uni-koeln.de

Received 20 November 2007; Revised 25 January 2008; Accepted 1 February 2008; Published online 20 March 2008.

Abstract

Nidogens have been proposed to play a key role in basement membrane (BM) formation. However, recent findings using genetic approaches and organotypic coculture models demonstrated distinct tissue requirements thus changing the classical view of BM assembly. Toward this end, we have analyzed the dermo-epidermal junction and the microvasculature in skin of nidogen-deficient mice for their BM composition and structural assembly. Histology of nidogen double-null embryos at embryonic day (E)18.5 revealed overall normal skin morphology with a regularly differentiated epidermis. However, in the dermis, numerous erythrocytes had extravasated out of the microvasculature. Residual composition and ultrastructure of the dermo-epidermal BM are not altered in the absence of nidogens, demonstrating that the deposition of laminin, collagen IV, and perlecan occurs and allows cutaneous BM formation. In contrast, in capillaries, BM formation is severely impaired in the absence of nidogens, showing an irregular, patchy distribution and a dramatically reduced deposition of collagen IV, perlecan, and particularly laminin-411. Ultrastructure revealed thin fragile walls in the small blood vessels next to the epidermis, completely lacking a distinct endothelial BM. In summary, our results indicate that in skin the laminin composition of the various BMs determines whether nidogens are required for their assembly and stabilization.