PUBLICATION
Systematic discovery of novel ciliary genes through functional genomics in the zebrafish
- Authors
- Choksi, S.P., Babu, D., Lau, D., Yu, X., Roy, S.
- ID
- ZDB-PUB-140821-3
- Date
- 2014
- Source
- Development (Cambridge, England) 141: 3410-9 (Journal)
- Registered Authors
- Choksi, Semil P., Roy, Sudipto
- Keywords
- Ciliary gene screen, Ciliopathy, Foxj1, Motile cilia, Primary ciliary dyskinesia, Zebrafish
- MeSH Terms
-
- Animals
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Organogenesis/drug effects
- Organogenesis/genetics
- Phenotype
- Gene Knockdown Techniques
- Zebrafish/embryology
- Zebrafish/genetics*
- Morpholinos/pharmacology
- Cilia/drug effects
- Cilia/genetics*
- Gene Expression Regulation, Developmental/drug effects
- Ciliary Motility Disorders/genetics
- Genomics*
- Up-Regulation/drug effects
- Up-Regulation/genetics
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Green Fluorescent Proteins/metabolism
- Forkhead Transcription Factors/genetics
- Forkhead Transcription Factors/metabolism
- Humans
- Genetic Association Studies*
- PubMed
- 25139857 Full text @ Development
Citation
Choksi, S.P., Babu, D., Lau, D., Yu, X., Roy, S. (2014) Systematic discovery of novel ciliary genes through functional genomics in the zebrafish. Development (Cambridge, England). 141:3410-9.
Abstract
Cilia are microtubule-based hair-like organelles that play many important roles in development and physiology, and are implicated in a rapidly expanding spectrum of human diseases, collectively termed ciliopathies. Primary ciliary dyskinesia (PCD), one of the most prevalent of ciliopathies, arises from abnormalities in the differentiation or motility of the motile cilia. Despite their biomedical importance, a methodical functional screen for ciliary genes has not been carried out in any vertebrate at the organismal level. We sought to systematically discover novel motile cilia genes by identifying the genes induced by Foxj1, a winged-helix transcription factor that has an evolutionarily conserved role as the master regulator of motile cilia biogenesis. Unexpectedly, we find that the majority of the Foxj1-induced genes have not been associated with cilia before. To characterize these novel putative ciliary genes, we subjected 50 randomly selected candidates to a systematic functional phenotypic screen in zebrafish embryos. Remarkably, we find that over 60% are required for ciliary differentiation or function, whereas 30% of the proteins encoded by these genes localize to motile cilia. We also show that these genes regulate the proper differentiation and beating of motile cilia. This collection of Foxj1-induced genes will be invaluable for furthering our understanding of ciliary biology, and in the identification of new mutations underlying ciliary disorders in humans.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping