Development, Vol 128, Issue 5 733-742, Copyright © 2001 by Company of Biologists

JOURNAL ARTICLES

An absolute requirement for Cubitus interruptus in Hedgehog signaling

N Methot and K Basler
Institut fur Molekularbiologie, Universitat Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

Hedgehog (Hh) proteins play diverse organizing roles in animal development by regulating gene expression in responding cells. Several components of the Hh signal transduction pathway have been identified, yet their precise role in mediating the various outputs of the pathway is still poorly understood. The Gli homolog Cubitus interruptus (Ci) is involved in controlling the transcription of Drosophila Hh target genes and thus represents the most downstream component known in this pathway. We address the question of whether the Hh pathway is distally branched or, in other words, whether the regulation of Ci activity is the sole output of Hh signaling. Putative Ci-independent branches of Hh signaling are explored by analyzing the behavior of cells that lack Ci but have undergone maximal activation of the Hh transduction pathway due to the removal of Patched (Ptc). The analysis of target gene expression and morphogenetic read-outs of Hh in embryonic, larval and adult stages indicates that Ci is absolutely required for all examined aspects of Hh outputs. We interpret this as evidence against the existence of Ci-independent branches in the Hh signal transduction pathway and propose that most cases of apparent Ci/Gli-independent Hh output can be attributed to the derepression of target gene expression in the absence of Ci/Gli repressor function.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Galletti, S. Riccardo, F. Parisi, C. Lora, M. K. Saqcena, L. Rivas, B. Wong, A. Serra, F. Serras, D. Grifoni, et al. Identification of Domains Responsible for Ubiquitin-Dependent Degradation of dMyc by Glycogen Synthase Kinase 3{beta} and Casein Kinase 1 Kinases Mol. Cell. Biol., June 15, 2009; 29(12): 3424 - 3434. [Abstract] [Full Text] [PDF]

				A. N. Hoover, A. Wynkoop, H. Zeng, J. Jia, L. A. Niswander, and A. Liu C2cd3 is required for cilia formation and Hedgehog signaling in mouse Development, December 15, 2008; 135(24): 4049 - 4058. [Abstract] [Full Text] [PDF]

				M. Varjosalo and J. Taipale Hedgehog signaling J. Cell Sci., January 1, 2007; 120(1): 3 - 6. [Full Text] [PDF]

				Q. Zhou, S. Apionishev, and D. Kalderon The Contributions of Protein Kinase A and Smoothened Phosphorylation to Hedgehog Signal Transduction in Drosophila melanogaster Genetics, August 1, 2006; 173(4): 2049 - 2062. [Abstract] [Full Text] [PDF]

				M. C. Hu, R. Mo, S. Bhella, C. W. Wilson, P.-T. Chuang, C.-c. Hui, and N. D. Rosenblum GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis Development, February 1, 2006; 133(3): 569 - 578. [Abstract] [Full Text] [PDF]

				E. G. Huntzicker, I. S. Estay, H. Zhen, L. A. Lokteva, P. K. Jackson, and A. E. Oro Dual degradation signals control Gli protein stability and tumor formation Genes & Dev., February 1, 2006; 20(3): 276 - 281. [Abstract] [Full Text] [PDF]

				L. Koziel, M. Wuelling, S. Schneider, and A. Vortkamp Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation Development, December 1, 2005; 132(23): 5249 - 5260. [Abstract] [Full Text] [PDF]

				V. Nguyen, A. L. Chokas, B. Stecca, and A. R. i Altaba Cooperative requirement of the Gli proteins in neurogenesis Development, July 15, 2005; 132(14): 3267 - 3279. [Abstract] [Full Text] [PDF]

				K. S. Ho, K. Suyama, M. Fish, and M. P. Scott Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused Development, March 15, 2005; 132(6): 1401 - 1412. [Abstract] [Full Text] [PDF]

				C. A. Callahan, T. Ofstad, L. Horng, J. K. Wang, H. H. Zhen, P. A. Coulombe, and A. E. Oro MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription Genes & Dev., November 15, 2004; 18(22): 2724 - 2729. [Abstract] [Full Text] [PDF]

				M. Merchant, F. F. Vajdos, M. Ultsch, H. R. Maun, U. Wendt, J. Cannon, W. Desmarais, R. A. Lazarus, A. M. de Vos, and F. J. de Sauvage Suppressor of Fused Regulates Gli Activity through a Dual Binding Mechanism Mol. Cell. Biol., October 1, 2004; 24(19): 8627 - 8641. [Abstract] [Full Text] [PDF]

				Q. Lei, A. K. Zelman, E. Kuang, S. Li, and M. P. Matise Transduction of graded Hedgehog signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord Development, August 1, 2004; 131(15): 3593 - 3604. [Abstract] [Full Text] [PDF]

				L. Lum and P. A. Beachy The Hedgehog Response Network: Sensors, Switches, and Routers Science, June 18, 2004; 304(5678): 1755 - 1759. [Abstract] [Full Text] [PDF]

				K. Sekimizu, N. Nishioka, H. Sasaki, H. Takeda, R. O. Karlstrom, and A. Kawakami The zebrafish iguana locus encodes Dzip1, a novel zinc-finger protein required for proper regulation of Hedgehog signaling Development, June 1, 2004; 131(11): 2521 - 2532. [Abstract] [Full Text] [PDF]

				O. V. Bulgakov, J. T. Eggenschwiler, D.-H. Hong, K. V. Anderson, and T. Li FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues Development, May 1, 2004; 131(9): 2149 - 2159. [Abstract] [Full Text] [PDF]

				L. Buttitta, R. Mo, C.-C. Hui, and C.-M. Fan Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction Development, December 22, 2003; 130(25): 6233 - 6243. [Abstract] [Full Text] [PDF]

				C. W. Larsen, E. Hirst, C. Alexandre, and J.-P. Vincent Segment boundary formation in Drosophila embryos Development, December 1, 2003; 130(23): 5625 - 5635. [Abstract] [Full Text] [PDF]

				L. Schweizer, D. Nellen, and K. Basler Requirement for Pangolin/dTCF in Drosophila Wingless signaling PNAS, May 13, 2003; 100(10): 5846 - 5851. [Abstract] [Full Text] [PDF]

				R. O. Karlstrom, O. V. Tyurina, A. Kawakami, N. Nishioka, W. S. Talbot, H. Sasaki, and A. F. Schier Genetic analysis of zebrafish gli1 and gli2 reveals divergent requirements for gli genes in vertebrate development Development, April 15, 2003; 130(8): 1549 - 1564. [Abstract] [Full Text] [PDF]

				C. B. Bai, W. Auerbach, J. S. Lee, D. Stephen, and A. L. Joyner Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway Development, March 12, 2003; 129(20): 4753 - 4761. [Abstract] [Full Text] [PDF]

				M. Persson, D. Stamataki, P. te Welscher, E. Andersson, J. Bose, U. Ruther, J. Ericson, and J. Briscoe Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity Genes & Dev., November 15, 2002; 16(22): 2865 - 2878. [Abstract] [Full Text] [PDF]

				P. te Welscher, A. Zuniga, S. Kuijper, T. Drenth, H. J. Goedemans, F. Meijlink, and R. Zeller Progression of Vertebrate Limb Development Through SHH-Mediated Counteraction of GLI3 Science, October 25, 2002; 298(5594): 827 - 830. [Abstract] [Full Text] [PDF]

				S. Barolo and J. W. Posakony Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling Genes & Dev., May 15, 2002; 16(10): 1167 - 1181. [Full Text] [PDF]

				J. Bai and D. Montell Eyes Absent, a key repressor of polar cell fate during Drosophila oogenesis Development, January 12, 2002; 129(23): 5377 - 5388. [Abstract] [Full Text] [PDF]

				C. B. Bai and A. L. Joyner Gli1 can rescue the in vivo function of Gli2 Development, December 15, 2001; 128(24): 5161 - 5172. [Abstract] [Full Text] [PDF]