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Updated: Sep 12, 2025

Using RNA-mediated Interference Feeding Strategy to Screen for Genes Involved in Body Size Regulation in the Nematode C. elegans
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Using RNA-mediated Interference Feeding Strategy to Screen for Genes Involved in Body Size Regulation in the Nematode C. elegans

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The CPEB ortholog Orb2 regulates brain size through the TRIM-NHL RNA-binding protein, Brain tumor

Taylor Hailstock1,2, Joseph Buehler1,2,3, Beverly V Robinson1,3,4

  • 1Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.

Biorxiv : the Preprint Server for Biology
|August 8, 2025
PubMed

Insights

The Drosophila CPEB protein Orb2 regulates brain size. Orb2

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Translational control is crucial for neurodevelopment.
  • Disruptions in translational regulation are linked to neurological disorders like intellectual disability and microcephaly.
  • The role of CPEB-family proteins in brain size regulation is not fully understood.

Purpose of the Study:

  • To investigate the function of the Drosophila CPEB-family protein Orb2 in neurodevelopment and brain size control.
  • To elucidate the mechanisms by which Orb2 influences neural stem cell development and brain growth.
  • To determine the structure-function relationships of Orb2 domains in regulating brain size.

Main Methods:

  • Genetic manipulation of Orb2 in Drosophila (loss-of-function and overexpression).
  • Analysis of larval brain size (hypotrophy and overgrowth).
  • Structure-function analysis of Orb2 domains (RNA-binding, poly-Q, ZZ).
  • Genetic and biochemical assays to identify Orb2 interacting partners and pathways, including Brain tumor (Brat).

Main Results:

  • Loss of Orb2 leads to larval brain hypotrophy (reduced size).
  • Orb2 overexpression results in brain overgrowth (increased size).
  • Orb2 is essential for neural stem cell development throughout Drosophila neurogenesis.
  • Orb2's RNA-binding activity promotes brain growth, while its poly-Q and ZZ domains restrain overgrowth.
  • Orb2 functions upstream of the translational repressor Brat, modulating Brat protein levels.
  • Orb2 and Brat exhibit antagonistic activities influencing brain size.

Conclusions:

  • Orb2 plays a critical, dose-dependent role in regulating Drosophila brain size.
  • Orb2's function involves both promoting and restraining growth through distinct domains and interactions.
  • The antagonistic interplay between Orb2 and Brat is essential for balanced brain growth during neurodevelopment.
Keywords:
brain growthmicrocephalymodels of human diseaseneurodevelopmentorgan size

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