Novel phenotypic elements of type IV collagenopathy revealed by the Drosophila model

András A. Kiss, Nikoletta Somlyai-Popovics, Vilmos Tubak, Z. Boldogkői, Katalin Csiszár, Mátyás Mink

Research output: Contribution to journalArticle

Abstract

Type IV collagen is proposed to be a key molecule in the evolvement of multicellular animals by forming the architectural unit basement membrane, a specialized form of the extracellular matrix. Functions of the basement membrane include guiding organ regeneration, tissue repair, modulation of cell differentiation, apical-basal polarity identification, cell migration and adhesion, regulation of growth factor signaling gradients, maintenance of tissue architecture and compartmentalization. Type IV collagenopathy is a devastating systemic disease affecting the circulatory, renal and visual systems and the skeletal muscles. It is observed in patients carrying mutations in the COL4A1 gene, which codes for the ubiquitous basement membrane component. Col4a1 mouse mutants display the human symptoms of type IV collagenopathy. We chose the Drosophila melanogaster model as we recorded dominant, temperature-sensitive mutations in the cognate col4a1 gene of the fruit fly and demonstrated phenotypic elements which have not yet been explored in humans or in mouse models. In this paper we show a transition of the Z-discs, normally bordering each sarcomere, to the level of M-discs significantly penetrant in the mutants, uneven distribution of fused mitochondria in the Malpighian tubules of the excretory organ and a loss of sarcomere structure in the visceral muscles in the gut of mutants. Our observations demonstrate the systemic nature of the col4a1 mutations in the fruit fly. However, these traits are elements of the type IV collagen-associated pathology and may provide insights into approaches that can alleviate symptoms of the disease.

Original languageEnglish
Article number2083
JournalApplied Sciences (Switzerland)
Volume9
Issue number10
DOIs
Publication statusPublished - May 1 2019

Fingerprint

Drosophila
mutations
basements
Collagen Type IV
fruits
collagens
Fruits
membranes
Collagen
organs
genes
mice
Muscle
Genes
circulatory system
penetrants
skeletal muscle
Tissue regeneration
Mitochondria
mitochondria

Keywords

  • Drosophila model
  • Multisystem disease
  • Mutation
  • Type IV collagen

ASJC Scopus subject areas

  • Materials Science(all)
  • Instrumentation
  • Engineering(all)
  • Process Chemistry and Technology
  • Computer Science Applications
  • Fluid Flow and Transfer Processes

Cite this

Novel phenotypic elements of type IV collagenopathy revealed by the Drosophila model. / Kiss, András A.; Somlyai-Popovics, Nikoletta; Tubak, Vilmos; Boldogkői, Z.; Csiszár, Katalin; Mink, Mátyás.

In: Applied Sciences (Switzerland), Vol. 9, No. 10, 2083, 01.05.2019.

Research output: Contribution to journalArticle

Kiss, András A. ; Somlyai-Popovics, Nikoletta ; Tubak, Vilmos ; Boldogkői, Z. ; Csiszár, Katalin ; Mink, Mátyás. / Novel phenotypic elements of type IV collagenopathy revealed by the Drosophila model. In: Applied Sciences (Switzerland). 2019 ; Vol. 9, No. 10.
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