PT  - JOURNAL ARTICLE
AU  - Georg Wolfstetter
AU  - Ina Dahlitz
AU  - Kathrin Pfeifer
AU  - Joscha Arne Alt
AU  - Uwe Töpfer
AU  - Daniel Christoph Pfeifer
AU  - Reinhard Lakes-Harlan
AU  - Stefan Baumgartner
AU  - Ruth H. Palmer
AU  - Anne Holz
TI  - Characterization of <em>Drosophila Nidogen/entactin</em> reveals roles in basement membrane stability, barrier function and nervous system plasticity
AID  - 10.1101/348631
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 348631
4099  - http://biorxiv.org/content/early/2018/06/18/348631.short
4100  - http://biorxiv.org/content/early/2018/06/18/348631.full
AB  - Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed of Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). While the essential and evolutionary conserved functions of Laminin, Collagen and Perlecan are well documented in Drosophila and other species, the proposed role of NDG as the major ECM linker molecule has been challenged by several in vivo studies revealing that NDG is dispensable for viability and BM formation. Here, we report the characterization of the single Ndg gene in Drosophila. Embryonic Ndg expression differed from that of other BM components and was primarily observed in mesodermal tissues and the chordotonal organs, whereas NDG protein localized to all BMs. While loss of Laminin strongly affected BM-localization of NDG, Ndg null mutants exhibited no overt changes in the distribution of BM core components. However, loss of NDG led to ultrastructural BM defects compromising barrier function and stability in vivo. Although Ndg mutants were viable, loss of NDG led to decreased fecundity in flies as well as impaired crawling behavior and reduced response to vibrational stimuli in larvae. Further morphological analysis revealed accompanying defects in the larval peripheral nervous system especially in the chordotonal organs and the neuromuscular junction (NMJ), where Ndg genetically interacted with the Leukocyte-antigen-related-like (Lar) receptor gene to regulate NMJ extension and synaptic differentiation. Taken together, our analysis suggests that NDG is not essential for BM assembly but mediates BM stability and ECM-dependent neural plasticity during Drosophila development.Summary Statement In this study we characterize Drosophila Nidogen/Entactin (Ndg) mutants revealing that loss of Ndg impairs basement membrane (BM) stability and permeability as well as proper function of the nervous system.