TY - JOUR
T1 - Basement membranes in skin are differently affected by lack of nidogen 1 and 2
AU - Mokkapati, Sharada
AU - Baranowsky, Anke
AU - Mirancea, Nicolae
AU - Smyth, Neil
AU - Breitkreutz, Dirk
AU - Nischt, Roswitha
N1 - Funding Information:
We thank all colleagues listed in “Materials and Methods” for providing antibodies and gratefully acknowledge the excellent technical assistance by Marion Reibetanz (Department of Dermatology, University of Cologne). Further, we thank Dr Ingrid Hauser (Department of Dermatology, University of Heidelberg) for her help with electron microscopy and Dr Paola Zigrino (Department of Dermatology, University of Cologne) for helpful discussion of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft through the SFB 589 at the University of Cologne (R.N.).
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2008.65
DO - 10.1038/jid.2008.65
M3 - Article
C2 - 18356808
AN - SCOPUS:49549122079
SN - 0022-202X
VL - 128
SP - 2259
EP - 2267
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -