Tgif1 and Tgif2 Repress Expression of the RabGAP Evi5l. Mol Cell Biol 2017 Mar 01;37(5)
Date
12/14/2016Pubmed ID
27956704Pubmed Central ID
PMC5311242DOI
10.1128/MCB.00527-16Scopus ID
2-s2.0-85013977866 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
Mouse embryos conditionally lacking Tgif1 and Tgif2 have holoprosencephaly and defects in left-right asymmetry. To identify pathways affected by loss of Tgif function during embryogenesis, we performed transcriptome profiling on whole mouse embryos. Among the genes with altered expression in embryos lacking Tgifs were a number with links to cilium function. One of these, Evi5l, encodes a RabGAP that is known to block the formation of cilia when overexpressed. Evi5l expression is increased in Tgif1; Tgif2-null embryos and in double-null mouse embryo fibroblasts (MEFs). Knockdown of Tgifs in a human retinal pigment epithelial cell line also increased EVI5L expression. We show that TGIF1 binds to a conserved consensus TGIF site 5' of the human and mouse Evi5l genes and represses Evi5l expression. In primary MEFs lacking both Tgifs, the number of cells with primary cilia was significantly decreased, and we observed a reduction in the transcriptional response to Shh pathway activation. Reducing Evi5l expression in MEFs lacking Tgifs resulted in a partial restoration of cilium numbers and in the transcriptional response to activation of the Shh pathway. In summary, this work shows that Tgifs regulate ciliogenesis and suggests that Evi5l mediates at least part of this effect.
Author List
Anderson AE, Taniguchi K, Hao Y, Melhuish TA, Shah A, Turner SD, Sutherland AE, Wotton DAuthor
Kenichiro Taniguchi PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Cilia
Embryo, Mammalian
GTPase-Activating Proteins
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Ontology
Hedgehog Proteins
Homeodomain Proteins
Humans
Mice
Mice, Knockout
Repressor Proteins
Signal Transduction
Transcription Factors
