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Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning

Journal article
Authors Georg Wolfstetter
I. Dahlitz
Kathrin Pfeifer
U. Topfer
J. A. Alt
D. C. Pfeifer
R. Lakes-Harlan
S. Baumgartner
R. H. Palmer
A. Holz
Published in Development
Volume 146
Issue 2
ISSN 0950-1991
Publication year 2019
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Links dx.doi.org/10.1242/dev.168948
Keywords Laminin, Collagen, Perlecan, Extracellular matrix, ECM, Muscle, Dorsal median cells, Axon guidance, collagen-iv, genetic-analysis, binding-sites, nidogen, laminin, protein, sequence, expression, chain, perlecan, Developmental Biology, iang c, 1994, development, v120, p3581, omczynski p, 1987, analytical biochemistry, v162, p156, rre c, 1992, journal of neuroscience research, v31, p146, x jw, 1991, embo journal, v10, p3137
Subject categories Developmental Biology

Abstract

Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed of Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). Recent in vivo studies challenged the initially proposed role of NDG as a major ECM linker molecule by revealing dispensability for viability and BM formation. Here, we report the characterization of the single Ndg gene in Drosophila. Embryonic Ndg expression was primarily observed in mesodermal tissues and the chordotonal organs, whereas NDG protein localized to all BMs. Although loss of Laminin strongly affected BM localization of NDG, Ndg-null mutants exhibited no overt changes in the distribution of BM components. Although Drosophila Ndg mutants were viable, loss of NDGled to ultrastructural BM defects that compromised barrier function and stability in vivo. Moreover, loss of NDG impaired larval crawling behavior and reduced responses to vibrational stimuli. Further morphological analysis revealed accompanying defects in the larval peripheral nervous system, especially in the chordotonal organs and the neuromuscular junction (NMJ). 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.

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