Cited by 99Genetic and Kidney Cyst DiseasesHedgehog Signaling Pathway StudiesCongenital heart defects research

Hippi is essential for node cilia assembly and Sonic hedgehog signaling

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Houde, Caroline, Dickinson, Robin J., Houtzager, Vicky M., Cullum, Rebecca, Montpetit, Rachel, Metzler, Martina, Simpson, Elizabeth M., Roy, Sophie +3 more·2006·Developmental Biology

Abstract

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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Crossref · 10.1016/j.ydbio.2006.09.001

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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)
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
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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