Hippi is essential for node cilia assembly and Sonic hedgehog signaling

• Published in: Developmental biology Vol. 300; no. 2; pp. 523 - 533
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2006
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Animals; Body Patterning - genetics; Central Nervous System - embryology; Cilia; Cilia - physiology; Female; Hedgehog Proteins - physiology; Hippi; Huntington disease; Left–right patterning; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction - physiology; Sonic hedgehog; Hippi; Sonic hedgehog; Left–right patterning; Huntington disease; Cilia
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2006.09.001

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.