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Linking pseudouridine synthases to growth, development and cell competition.

Giuseppe Tortoriello1, José F de Celis, Maria Furia

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Summary

Loss of pseudouridine synthase (mfl) in Drosophila wings causes cell death and developmental defects. This phenotype is linked to impaired Notch signaling, impacting wing patterning and cell differentiation.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Pseudouridine synthases modify RNA, and their dysfunction in humans causes dyskeratosis congenita.
  • H/ACA small nucleolar RNAs (snoRNAs) are bound by pseudouridine synthases and may form microRNA-like molecules.
  • Understanding pseudouridine synthase function is crucial for deciphering cellular consequences of its failure.

Purpose of the Study:

  • To investigate the function of the pseudouridine synthase gene minifly (mfl) in Drosophila wing development using a loss-of-function approach.
  • To elucidate the molecular mechanisms underlying the effects of mfl depletion on cell growth, differentiation, and tissue patterning.

Main Methods:

  • Loss-of-function analysis of the mfl gene in Drosophila wing discs.
  • Assessment of cell number, cell size, proliferation, and apoptosis.
  • Investigation of wing patterning, lineage boundaries, and cell differentiation.
  • Analysis of potential links to Notch signaling pathways.

Main Results:

  • Depletion of mfl significantly reduced wing size by decreasing cell number and size.
  • Reduced cell number was primarily due to apoptosis, not reduced proliferation.
  • mfl silencing led to cell elimination in mosaic tissues via cell competition.
  • mfl loss disrupted wing patterning, lineage boundaries, and margin formation, mimicking reduced Notch activity.

Conclusions:

  • Pseudouridine synthase deficiency in Drosophila wings triggers apoptosis and affects cell competition.
  • The loss of mfl function impacts wing development and patterning, suggesting a role in Notch signaling.
  • These findings highlight the importance of pseudouridine synthases in developmental processes and cellular homeostasis.