Nidogen-1 or -2 Promote Basement Membrane Formation in Skin -Type 3D-Cocultures

2004 ◽  
Vol 2004 (Fall) ◽  
Author(s):  
Eva C. Woenne ◽  
Cathrine Schmidt ◽  
Nick Mirancea ◽  
Roswitha Nischt ◽  
Neil Smyth ◽  
...  
2012 ◽  
Vol 26 (9) ◽  
pp. 3637-3648 ◽  
Author(s):  
Manuela Bechtel ◽  
Manuel V. Keller ◽  
Wilhelm Bloch ◽  
Takako Sasaki ◽  
Petra Boukamp ◽  
...  

2002 ◽  
Vol 22 (19) ◽  
pp. 6820-6830 ◽  
Author(s):  
Jürgen Schymeinsky ◽  
Sabine Nedbal ◽  
Nicolai Miosge ◽  
Ernst Pöschl ◽  
Cherie Rao ◽  
...  

ABSTRACT Nidogens are highly conserved proteins in vertebrates and invertebrates and are found in almost all basement membranes. According to the classical hypothesis of basement membrane organization, nidogens connect the laminin and collagen IV networks, so stabilizing the basement membrane, and integrate other proteins. In mammals two nidogen proteins, nidogen-1 and nidogen-2, have been discovered. Nidogen-2 is typically enriched in endothelial basement membranes, whereas nidogen-1 shows broader localization in most basement membranes. Surprisingly, analysis of nidogen-1 gene knockout mice presented evidence that nidogen-1 is not essential for basement membrane formation and may be compensated for by nidogen-2. In order to assess the structure and in vivo function of the nidogen-2 gene in mice, we cloned the gene and determined its structure and chromosomal location. Next we analyzed mice carrying an insertional mutation in the nidogen-2 gene that was generated by the secretory gene trap approach. Our molecular and biochemical characterization identified the mutation as a phenotypic null allele. Nidogen-2-deficient mice show no overt abnormalities and are fertile, and basement membranes appear normal by ultrastructural analysis and immunostaining. Nidogen-2 deficiency does not lead to hemorrhages in mice as one may have expected. Our results show that nidogen-2 is not essential for basement membrane formation or maintenance.


2000 ◽  
Vol 20 (18) ◽  
pp. 7007-7012 ◽  
Author(s):  
Monzur Murshed ◽  
Neil Smyth ◽  
Nicolai Miosge ◽  
Jörg Karolat ◽  
Thomas Krieg ◽  
...  

ABSTRACT Nidogen 1 is a highly conserved protein in mammals,Drosophila melanogaster, Caenorhabditis elegans, and ascidians and is found in all basement membranes. It has been proposed that nidogen 1 connects the laminin and collagen IV networks, so stabilizing the basement membrane, and integrates other proteins, including perlecan, into the basement membrane. To define the role of nidogen 1 in basement membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic stem cells and used these to derive mouse lines. Homozygous animals produce neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt abnormalities and are fertile, their basement membrane structures appearing normal. Nidogen 2 staining is increased in certain basement membranes, where it is normally only found in scant amounts. This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated. The results show that nidogen 1 is not required for basement membrane formation or maintenance.


Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2711-2722 ◽  
Author(s):  
Michael Willem ◽  
Nicolai Miosge ◽  
Willi Halfter ◽  
Neil Smyth ◽  
Iris Jannetti ◽  
...  

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, γ1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.


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