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

Development. 2019 Jan 16;146(2):dev168948. doi: 10.1242/dev.168948.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism*
  • Basement Membrane / ultrastructure
  • Behavior, Animal
  • Biomechanical Phenomena
  • Body Patterning*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / genetics
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Laminin / metabolism
  • Larva / genetics
  • Nervous System / embryology*
  • Nervous System / metabolism*
  • Neuromuscular Junction / pathology
  • Peripheral Nervous System / embryology
  • Peripheral Nervous System / pathology
  • Permeability
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vibration


  • Calcium-Binding Proteins
  • Drosophila Proteins
  • Extracellular Matrix Proteins
  • Laminin
  • Ndg protein, Drosophila
  • RNA, Messenger