PUBLICATION
Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine
- Authors
- Makky, K., Tekiela, J., and Mayer, A.N.
- ID
- ZDB-PUB-070210-1
- Date
- 2007
- Source
- Developmental Biology 303(2): 501-513 (Journal)
- Registered Authors
- Mayer, Alan
- Keywords
- Intestine, Target of rapamycin, mTOR, TORC1, Zebrafish, Organogenesis, Morphogenesis, Intestinal development
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Base Sequence
- DNA Primers/genetics
- Embryonic Development/drug effects
- Embryonic Development/genetics
- Embryonic Development/physiology
- Epithelium/drug effects
- Epithelium/embryology
- Epithelium/metabolism
- Gene Expression Regulation, Developmental
- Intestines/drug effects
- Intestines/embryology*
- Intestines/metabolism*
- Morphogenesis
- Protein Kinases/genetics
- Protein Kinases/metabolism*
- Signal Transduction
- Sirolimus/pharmacology
- TOR Serine-Threonine Kinases
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 17222402 Full text @ Dev. Biol.
Citation
Makky, K., Tekiela, J., and Mayer, A.N. (2007) Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine. Developmental Biology. 303(2):501-513.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping