PUBLICATION

Dissecting the Functional Interplay Between the TOR Pathway and the Cilium in Zebrafish

Authors
Yuan, S., Zhao, L., and Sun, Z.
ID
ZDB-PUB-130408-18
Date
2013
Source
Methods in enzymology   525: 159-189 (Chapter)
Registered Authors
Sun, Zhaoxia, Yuan, Shiaulou
Keywords
cilium, mechanistic target-of-rapamycin, tuberous sclerosis complex, S6K1, laterality, flagella
MeSH Terms
  • Animals
  • Cilia/metabolism*
  • Cilia/physiology
  • Embryo, Nonmammalian/metabolism
  • Flagella/metabolism
  • Flagella/physiology
  • Gene Expression Regulation, Developmental
  • Multiprotein Complexes/metabolism
  • TOR Serine-Threonine Kinases/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed
23522470 Full text @ Methods Enzymol.
Abstract

The target-of-rapamycin (TOR) pathway is a major regulator of cellular growth, division, and metabolism by coupling growth and nutrient cues to fundamental processes such as translation and transcription. In vertebrate models, disruptions affecting components of the TOR pathway result in cilia size abnormalities and ciliopathic phenotypes such as renal cysts. However, the mechanism by which the TOR pathway influenced cilia length and function was unknown. Recent work from zebrafish, in conjunction with the green alga Chlamydomonas, demonstrates that TOR complex 1 (TORC1)-mediated cilia length control is achieved through translational regulation of ciliary precursors. Further, in zebrafish, aberrant TORC1 signaling leads to left–right asymmetric patterning defects due to inefficient ciliary motility and fluid flow generation in the Kupffer's vesicle, a conserved embryonic organ that establishes laterality. Together, such findings show the utility of a combinatorial zebrafish and Chlamydomonas approach to dissecting the mechanistic relationship between the cilium and signaling molecules such as TOR. Here, we describe tools, reagents, and methodologies for the manipulation of the TOR pathway and the analysis of cilia morphology and function in zebrafish and Chlamydomonas.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping