Hippi is essential for node cilia assembly and Sonic hedgehog signaling

Houde, Caroline; Dickinson, Robin J.; Houtzager, Vicky M.; Cullum, Rebecca; Montpetit, Rachel; Metzler, Martina; Simpson, Elizabeth M.; Roy, Sophie; Hayden, Michael R.; Hoodless, Pamela A.; Nicholson, Donald W.

doi:10.1016/j.ydbio.2006.09.001

Cited by 85 publications

(85 citation statements)

References 69 publications

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“…In the ciliate Tetrahymena thermophila, knockout of IFT172 or depletion of IFT80 leads to strong ciliary assembly defects (Beales et al , 2007; Tsao & Gorovsky, 2008), and mutations or depletions of IFT80, IFT172, IFT57, IFT54 (elipsa), and IFT38 (qilin) disrupt ciliogenesis and lead to cystic kidneys and curled body axis in zebrafish (Sun et al , 2004; Beales et al , 2007; Omori et al , 2008; Lunt et al , 2009). Most importantly, knockout mice for IFT172 (wimple), IFT57 (Hippi), IFT54 (Traf3IP/MIP‐T3), IFT38 (Cluap1), IFT20, and IFT80 display embryonic lethality highlighting their essential roles in ciliogenesis in mammals (Huangfu et al , 2003; Houde et al , 2006; Jonassen et al , 2008; Berbari et al , 2011; Rix et al , 2011; Pasek et al , 2012). How the peripheral IFT‐B components associate with the core to form a functional IFT‐B complex is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

et al. 2016

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Intraflagellar transport (IFT) relies on the IFT complex and is required for ciliogenesis. The IFT‐B complex consists of 9–10 stably associated core subunits and six “peripheral” subunits that were shown to dissociate from the core structure at moderate salt concentration. We purified the six “peripheral” IFT‐B subunits of Chlamydomonas reinhardtii as recombinant proteins and show that they form a stable complex independently of the IFT‐B core. We suggest a nomenclature of IFT‐B1 (core) and IFT‐B2 (peripheral) for the two IFT‐B subcomplexes. We demonstrate that IFT88, together with the N‐terminal domain of IFT52, is necessary to bridge the interaction between IFT‐B1 and B2. The crystal structure of IFT52N reveals highly conserved residues critical for IFT‐B1/IFT‐B2 complex formation. Furthermore, we show that of the three IFT‐B2 subunits containing a calponin homology (CH) domain (IFT38, 54, and 57), only IFT54 binds αβ‐tubulin as a potential IFT cargo, whereas the CH domains of IFT38 and IFT57 mediate the interaction with IFT80 and IFT172, respectively. Crystal structures of IFT54 CH domains reveal that tubulin binding is mediated by basic surface‐exposed residues.

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Section: Introductionmentioning

confidence: 99%

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

et al. 2016

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“…I have also asked, is there any effect of animal model on the penetrance of LR defects? Importantly, when collecting this data, it was also apparent that many studies examine only asymmetric gene expression and use this data to make conclusions about organ position [see for example (Oki et al, 2010; Antic et al, 2010; Vick et al, 2009; Pathak et al, 2007; Houde et al, 2006; Kramer-Zucker et al, 2005; Zhang et al, 2001)]. A few studies have proposed that gene expression can be used to predict organ laterality, but the mathematical models produced to date have only been applied to extremely limited datasets (Ibanes and Izpisua Belmonte, 2009; Lohr et al, 1997; Mogi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Laterality defects are influenced by timing of treatments and animal model

Vandenberg

2012

Differentiation

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The timing of when the embryonic left-right (LR) axis is first established and the mechanisms driving this process are subjects of strong debate. While groups have focused on the role of cilia in establishing the LR axis during gastrula and neurula stages, many animals appear to orient the LR axis prior to the appearance of, or without the benefit of, motile cilia. Because of the large amount of data available in the published literature and the similarities in the type of data collected across labs, I have examined relationships between the studies that do and do not implicate cilia, the choice of animal model, the kinds of LR patterning defects observed, and the penetrance of LR phenotypes. I found that treatments affecting cilia structure and motility had a higher penetrance for both altered gene expression and improper organ placement compared to treatments that affect processes in early cleavage stage embryos. I also found differences in penetrance that could be attributed to the animal models used; the mouse is highly prone to LR randomization. Additionally, the data were examined to address whether gene expression can be used to predict randomized organ placement. Using regression analysis, gene expression was found to be predictive of organ placement in frogs, but much less so in the other animals examined. Together, these results challenge previous ideas about the conservation of LR mechanisms, with the mouse model being significantly different from fish, frogs and chick in almost every aspect examined. Additionally, this analysis indicates that there may be missing pieces in the molecular pathways that dictate how genetic information becomes organ positional information in vertebrates; these gaps will be important for future studies to identify, as LR asymmetry is not only a fundamentally fascinating aspect of development but also of considerable biomedical importance.

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“…Conventional Ift57 and Kif3a/ Kif3b null mutations in mice lead to early embryonic lethality due to left-right axis defects, accompanied by a loss of nodal cilia (14)(15)(16), suggesting that the IFT-B complex is critical for ciliogenesis. Supporting this idea, the deletion of Ift20 in mouse kidney causes a lack of primary cilia and leads to polycystic kidney disease (17).…”

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confidence: 99%

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

Noda¹,

Kitami²,

Kitami

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The primary cilium is a cellular organelle that coordinates signaling pathways critical for cell proliferation, differentiation, survival, and homeostasis. Intraflagellar transport (IFT) plays a pivotal role in assembling primary cilia. Disruption and/or dysfunction of IFT components can cause multiple diseases, including skeletal dysplasia. However, the mechanism by which IFT regulates skeletogenesis remains elusive. Here, we show that a neural crest-specific deletion of intraflagellar transport 20 (Ift20) in mice compromises ciliogenesis and intracellular transport of collagen, which leads to osteopenia in the facial region. Whereas platelet-derived growth factor receptor alpha (PDGFRα) was present on the surface of primary cilia in wildtype osteoblasts, disruption of Ift20 down-regulated PDGFRα production, which caused suppression of PDGF-Akt signaling, resulting in decreased osteogenic proliferation and increased cell death. Although osteogenic differentiation in cranial neural crest (CNC)-derived cells occurred normally in Ift20-mutant cells, the process of mineralization was severely attenuated due to delayed secretion of type I collagen. In control osteoblasts, procollagen was easily transported from the endoplasmic reticulum (ER) to the Golgi apparatus. By contrast, despite having similar levels of collagen type 1 alpha 1 (Col1a1) expression, Ift20 mutants did not secrete procollagen because of dysfunctional ER-to-Golgi trafficking. These data suggest that in the multipotent stem cells of CNCs, IFT20 is indispensable for regulating not only ciliogenesis but also collagen intracellular trafficking. Our study introduces a unique perspective on the canonical and noncanonical functions of IFT20 in craniofacial skeletal development.cranial neural crest cells | intracellular trafficking | intraflagellar transport | PDGF signaling | primary cilia

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Hippi is essential for node cilia assembly and Sonic hedgehog signaling

Cited by 85 publications

References 69 publications

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex

Laterality defects are influenced by timing of treatments and animal model

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

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