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

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Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning. / Wolfstetter, Georg; Dahlitz, Ina; Pfeifer, Kathrin; Töpfer, Uwe; Alt, Joscha Arne; Pfeifer, Daniel Christoph; Lakes-Harlan, Reinhard; Baumgartner, Stefan; Palmer, Ruth H.; Holz, Anne.

I: Development (Cambridge), Vol. 146, Nr. 2, 2019.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Wolfstetter, Georg ; Dahlitz, Ina ; Pfeifer, Kathrin ; Töpfer, Uwe ; Alt, Joscha Arne ; Pfeifer, Daniel Christoph ; Lakes-Harlan, Reinhard ; Baumgartner, Stefan ; Palmer, Ruth H. ; Holz, Anne. / Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning. I: Development (Cambridge). 2019 ; Vol. 146, Nr. 2.

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TY - JOUR

T1 - Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning

AU - Wolfstetter, Georg

AU - Dahlitz, Ina

AU - Pfeifer, Kathrin

AU - Töpfer, Uwe

AU - Alt, Joscha Arne

AU - Pfeifer, Daniel Christoph

AU - Lakes-Harlan, Reinhard

AU - Baumgartner, Stefan

AU - Palmer, Ruth H.

AU - Holz, Anne

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Axon guidance

KW - Collagen

KW - Dorsal median cells

KW - ECM

KW - Extracellular matrix

KW - Laminin

KW - Morphogenesis

KW - Muscle

KW - NMJ

KW - Perlecan

U2 - 10.1242/dev.168948

DO - 10.1242/dev.168948

M3 - Article

VL - 146

JO - Development: For advances in developmental biology and stem cells

JF - Development: For advances in developmental biology and stem cells

SN - 1477-9129

IS - 2

ER -