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Updated: Jul 17, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine
Khadijah Makky1, Jackie Tekiela, Alan N Mayer
1Gastroenterology Section, Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Abstract:
The target of rapamycin (TOR) signaling pathway regulates cell growth and proliferation, however the extent to which TOR signaling mediates particular organogenesis programs remains to be determined. Here we report an examination of TOR signaling during zebrafish development, using a combination of small molecule treatment and morpholino-mediated gene knockdown. First, we amplified and sequenced the full-length cDNA for the zebrafish TOR ortholog (ztor). By in situ hybridization, we found that ztor is expressed ubiquitously in the early embryo, but displays a dynamic pattern in the gut between 48 and 72 h post-fertilization (hpf). Treatment of zebrafish embryos with rapamycin induced only a mild general developmental delay up to 72 hpf, but digestive tract development became arrested at the primitive gut tube stage. Rapamycin inhibited intestinal epithelial growth, morphogenesis and differentiation. Using morpholino-mediated gene knockdown of TOR pathway components, we show that this effect is mediated specifically by the rapamycin-sensitive TOR complex 1 (TORC1). Thus, in addition to regulating cell growth and proliferation, TOR signaling controls the developmental program guiding epithelial morphogenesis in the vertebrate intestine.
Insights
Target of rapamycin (TOR) signaling controls zebrafish digestive tract development. Inhibition of TOR complex 1 (TORC1) specifically arrests intestinal morphogenesis and epithelial growth.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The target of rapamycin (TOR) pathway is crucial for cell growth and proliferation.
- Its role in specific organogenesis, particularly during vertebrate development, requires further elucidation.
Purpose of the Study:
- To investigate the function of TOR signaling in zebrafish organogenesis.
- To determine the specific TOR complex mediating developmental effects in the intestine.
Main Methods:
- Full-length zebrafish TOR (ztor) cDNA amplification and sequencing.
- In situ hybridization to analyze ztor expression patterns.
- Zebrafish embryo treatment with rapamycin (TOR inhibitor).
- Morpholino-mediated knockdown of TOR pathway components.
Main Results:
- Zebrafish TOR (ztor) is ubiquitously expressed early, with dynamic gut expression between 48-72 hours post-fertilization.
- Rapamycin treatment arrested digestive tract development at the primitive gut tube stage, inhibiting intestinal epithelial growth, morphogenesis, and differentiation.
- Knockdown experiments confirmed that TOR complex 1 (TORC1) mediates these effects.
Conclusions:
- TOR signaling is essential for vertebrate intestinal epithelial morphogenesis.
- TOR complex 1 (TORC1) specifically regulates intestinal development beyond general cell growth and proliferation.
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