Hippi is essential for node cilia assembly and Sonic hedgehog signaling
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Hippi functions as an adapter protein that mediates pro-apoptotic signaling from poly-glutamine-expanded huntingtin, an established cause of Huntington disease, to the extrinsic cell death pathway. To explore other functions of Hippi we generated Hippi knock-out mice. This deletion causes randomization of the embryo turning process and heart looping, which are hallmarks of defective left-right (LR) axis patterning. We report that motile monocilia normally present at the surface of the embryonic node, and proposed to initiate the break in LR symmetry, are absent on Hippi-/- embryos. Furthermore, defects in central nervous system development are observed. The Sonic hedgehog (Shh) pathway is downregulated in the neural tube in the absence of Hippi, which results in failure to establish ventral neural cell fate. Together, these findings demonstrate a dual role for Hippi in cilia assembly and Shh signaling during development, in addition to its proposed role in apoptosis signal transduction in the adult brain under pathogenically stressful conditions.
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The canonical Shh signaling cascade relies on the primary cilium for signal transduction.
“The canonical Shh signaling cascade relies on the primary cilium for signal transduction [25, 29–34].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [30]
In mammals, the canonical Shh signaling pathway requires primary cilia.
“In mammals, this canonical Shh signaling pathway requires primary cilia [25, 29–34].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [30]
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- Authors
- Houde, C., Dickinson, R. J., Houtzager, V. M., Cullum, R., Montpetit, R., Metzler, M., Simpson, E. M., Roy, S., Hayden, M. R., Hoodless, P. A., & Nicholson, D. W.
- Affiliations
- McGill University (CA)
- BC Cancer Agency (CA)
- Child and Family Research Institute (CA)
- University of British Columbia (CA)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Nicholson, Donald W.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 300
- Issue
- 2
- Pages
- 523-533
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC5053816
- OpenAlex
- W2038933392
- Cited by
- 98
- References
- 70
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 4 · 2013: 3 · 2012: 7
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Michael Smith Health Research BC
- Terry Fox Foundation
- University of British Columbia
- Canadian Institutes of Health Research (89806_1)
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- HIPPI, Sonic hedgehog signaling, embryonic node, heart looping, central nervous system development, neural tube, huntingtin, apoptosis, knockout mice
- MeSH terms
- Animals, Central Nervous System, Cilia, Female, Male, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Body Patterning, Adaptor Proteins, Signal Transducing, Mice, Hedgehog Proteins
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