Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,591 bioRxiv papers from 298,067 authors.

Genetic interaction of mammalian IFT-A paralogs regulates cilia disassembly, ciliary protein trafficking, Hedgehog signaling and embryogenesis

By Wei Wang, Bailey A Allard, Tana S Pottorf, Jay L Vivian, Pamela V Tran

Posted 13 Oct 2019
bioRxiv DOI: 10.1101/803544

Primary cilia are sensory organelles that are essential for eukaryotic development and health. These antenna-like structures are synthesized by intraflagellar transport protein complexes, IFT-B and IFT-A, which mediate bi-directional protein trafficking along the ciliary axoneme. Here using mouse embryonic fibroblasts (MEF), we investigate the ciliary roles of two mammalian orthologues of Chlamydomonas IFT-A gene, IFT139, namely Thm1 (also known as Ttc21b) and Thm2 (Ttc21a). Thm1 loss causes perinatal lethality, and Thm2 loss allows survival into adulthood. At E14.5, the number of Thm1;Thm2 double mutant embryos is lower than that for a Mendelian ratio, indicating deletion of Thm1 and Thm2 causes mid-gestational lethality. We examined the ciliary phenotypes of mutant MEF. Thm1-mutant MEF show decreased cilia assembly, shortened primary cilia, a retrograde IFT defect for IFT and BBS proteins, and reduced ciliary entry of membrane-associated proteins. Thm1-mutant cilia also show a retrograde transport defect for the Hedgehog transducer, Smoothened, and an impaired response to Smoothened agonist, SAG. Thm2-null MEF show normal ciliary dynamics and Hedgehog signaling, but additional loss of a Thm1 allele impairs response to SAG. Further, Thm1;Thm2 double mutant MEF show enhanced cilia disassembly, and relative to Thm1-null MEF, increased impairment of IFT81 retrograde transport and of INPP5E ciliary import. Thus, Thm1 and Thm2 have unique and redundant roles in MEF. Thm1 regulates cilia assembly, and together with Thm2, cilia disassembly. Moreover, Thm1 alone and together with Thm2, regulates ciliary protein trafficking, Hedgehog signaling, and embryogenesis. These findings shed light on mechanisms underlying Thm1-, Thm2- or IFT-A-mediated ciliopathies.

Download data

  • Downloaded 102 times
  • Download rankings, all-time:
    • Site-wide: 62,179 out of 67,591
    • In genetics: 3,558 out of 3,799
  • Year to date:
    • Site-wide: 48,976 out of 67,591
  • Since beginning of last month:
    • Site-wide: 18,409 out of 67,591

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide

Sign up for the Rxivist weekly newsletter! (Click here for more details.)