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

Development. 2019 Jan 16;146(2)
Georg Wolfstetter 1 , Ina Dahlitz 2 , Kathrin Pfeifer 1 , Uwe Töpfer 2 , Joscha Arne Alt 3 , Daniel Christoph Pfeifer 2 , Reinhard Lakes-Harlan 3 , Stefan Baumgartner 4 , Ruth H Palmer 1 , Anne Holz 5
Georg Wolfstetter 1 , Ina Dahlitz 2 , Kathrin Pfeifer 1 , Uwe Töpfer 2 , Joscha Arne Alt 3 , Daniel Christoph Pfeifer 2 , Reinhard Lakes-Harlan 3 , Stefan Baumgartner 4 , Ruth H Palmer 1 , Anne Holz 5
+ et al

[No authors listed]

Author information
  • 1 The Sahlgrenska Academy at the University of Gothenburg, Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, Medicinaregatan 9A, 41390 Gothenburg, Sweden.
  • 2 Justus-Liebig-Universitaet Giessen, Institut für Allgemeine und Spezielle Zoologie, Allgemeine Zoologie und Entwicklungsbiologie, Stephanstraße 24, 35390 Gießen, Germany.
  • 3 Justus-Liebig-Universitaet Giessen, Institut für Tierphysiologie, Integrative Sinnesphysiologie, Heinrich-Buff-Ring 26, 35392 Gießen, Germany.
  • 4 Lund University, Department of Experimental Medical Sciences, BMC D10, 22184 Lund, Sweden.
  • 5 Justus-Liebig-Universitaet Giessen, Institut für Allgemeine und Spezielle Zoologie, Allgemeine Zoologie und Entwicklungsbiologie, Stephanstraße 24, 35390 Gießen, Germany anne.holz@allzool.bio.uni-giessen.de.

摘要


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 NDG led 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.

KEYWORDS: Axon guidance, Collagen, Dorsal median cells, ECM, Extracellular matrix, Laminin, Morphogenesis, Muscle, NMJ, Perlecan