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Development, Vol 126, Issue 17 3915-3924, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
H Sasaki, Y Nishizaki, C Hui, M Nakafuku and H Kondoh
Laboratory of Developmental Biology, Institute for Molecular and Cellular Biology, Osaka University, Suita, Osaka 565-0871, Japan. hsasaki@imcb.osaka-u.ac.jp
Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling in vertebrates. The question remains unanswered, however, as to how these Gli proteins participate in the Shh signaling pathway. In this study, regulatory activities associated with the Gli2 protein were investigated in relation to the Shh signaling. Although Gli2 acts as a weak transcriptional activator, it is in fact a composite of positive and negative regulatory domains. In cultured cells, truncation of the activation domain in the C-terminal half results in a protein with repressor activity, while removal of the repression domain at the N terminus converts Gli2 into a strong activator. In transgenic mouse embryos, N-terminally truncated Gli2, unlike the full length protein, activates a Shh target gene, HNF3beta, in the dorsal neural tube, thus mimicking the effect of Shh signal. This suggests that unmasking of the strong activation potential of Gli2 through modulation of the N-terminal repression domain is one of the key mechanisms of the Shh signaling. A similar regulatory mechanism involving the N-terminal region was also found for Gli3, but not for Gli1. When the Shh signal derived from the notochord is received by the neural plate, the widely expressed Gli2 and Gli3 proteins are presumably converted to their active forms in the ventral cells, leading to activation of transcription of their target genes, including Gli1.
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 D. O. Walterhouse, M. L.G. Lamm, E. Villavicencio, and P. M. Iannaccone Emerging Roles for Hedgehog-Patched-Gli Signal Transduction in Reproduction Biol Reprod, July 1, 2003; 69(1): 8 - 14. [Abstract] [Full Text] [PDF]
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P. J. Ebert, J. R. Timmer, Y. Nakada, A. W. Helms, P. B. Parab, Y. Liu, T. L. Hunsaker, and J. E. Johnson Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation Development, May 1, 2003; 130(9): 1949 - 1959. [Abstract] [Full Text] [PDF]
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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]
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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]
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M. Takahashi and N. Osumi Pax6 regulates specification of ventral neurone subtypes in the hindbrain by establishing progenitor domains Development, March 5, 2003; 129(6): 1327 - 1338. [Abstract] [Full Text] [PDF]
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P. Mill, R. Mo, H. Fu, M. Grachtchouk, P. C.W. Kim, A. A. Dlugosz, and C.-c. Hui Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development Genes & Dev., January 15, 2003; 17(2): 282 - 294. [Abstract] [Full Text] [PDF]
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A. M. Kenney, M. D. Cole, and D. H. Rowitch Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors Development, January 1, 2003; 130(1): 15 - 28. [Abstract] [Full Text] [PDF]
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P. Dai, T. Shinagawa, T. Nomura, J. Harada, S. C. Kaul, R. Wadhwa, M. M. Khan, H. Akimaru, H. Sasaki, C. Colmenares, et al. Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3 Genes & Dev., November 15, 2002; 16(22): 2843 - 2848. [Abstract] [Full Text] [PDF]
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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]
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H. Sheng, S. Goich, A. Wang, M. Grachtchouk, L. Lowe, R. Mo, K. Lin, F. J. de Sauvage, H. Sasaki, C.-c. Hui, et al. Dissecting the Oncogenic Potential of Gli2: Deletion of an NH2-Terminal Fragment Alters Skin Tumor Phenotype Cancer Res., September 15, 2002; 62(18): 5308 - 5316. [Abstract] [Full Text] [PDF]
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B. K. Brott and S. Y. Sokol Regulation of Wnt/LRP Signaling by Distinct Domains of Dickkopf Proteins Mol. Cell. Biol., September 1, 2002; 22(17): 6100 - 6110. [Abstract] [Full Text] [PDF]
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Y.-S. Kim, M. Lewandoski, A. O. Perantoni, S. Kurebayashi, G. Nakanishi, and A. M. Jetten Identification of Glis1, a Novel Gli-related, Kruppel-like Zinc Finger Protein Containing Transactivation and Repressor Functions J. Biol. Chem., August 16, 2002; 277(34): 30901 - 30913. [Abstract] [Full Text] [PDF]
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Y. Huang, H. Roelink, and G. S. McKnight Protein Kinase A Deficiency Causes Axially Localized Neural Tube Defects in Mice J. Biol. Chem., May 24, 2002; 277(22): 19889 - 19896. [Abstract] [Full Text] [PDF]
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F. Zhang, G. Nakanishi, S. Kurebayashi, K. Yoshino, A. Perantoni, Y.-S. Kim, and A. M. Jetten Characterization of Glis2, a Novel Gene Encoding a Gli-related, Kruppel-like Transcription Factor with Transactivation and Repressor Functions. ROLES IN KIDNEY DEVELOPMENT AND NEUROGENESIS J. Biol. Chem., March 15, 2002; 277(12): 10139 - 10149. [Abstract] [Full Text] [PDF]
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M. K. Gustafsson, H. Pan, D. F. Pinney, Y. Liu, A. Lewandowski, D. J. Epstein, and C. P. Emerson Jr. Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification Genes & Dev., January 1, 2002; 16(1): 114 - 126. [Abstract] [Full Text] [PDF]
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 N. Sato, P. L. Leopold, and R. G. Crystal Effect of Adenovirus-Mediated Expression of Sonic Hedgehog Gene on Hair Regrowth in Mice With Chemotherapy-Induced Alopecia J Natl Cancer Inst, December 19, 2001; 93(24): 1858 - 1864. [Abstract] [Full Text] [PDF]
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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]
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R. Mo, J. H. Kim, J. Zhang, C. Chiang, C.-c. Hui, and P. C. W. Kim Anorectal Malformations Caused by Defects in Sonic Hedgehog Signaling Am. J. Pathol., August 1, 2001; 159(2): 765 - 774. [Abstract] [Full Text]
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 R. H. Costa, V. V. Kalinichenko, and L. Lim Transcription factors in mouse lung development and function Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L823 - L838. [Abstract] [Full Text] [PDF]
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 K. J. Fryxell, M. Soderlund, T. V. Jordan, J. M. Verdi, and C. J. Kubu An Animal Model for the Molecular Genetics of CADASIL Stroke, January 1, 2001; 32(1): 6 - 11. [Abstract] [Full Text] [PDF]
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A. Borycki, A. M. Brown, and C. P. Emerson Shh and Wnt signaling pathways converge to control Gli gene activation in avian somites Development, May 15, 2000; 127(10): 2075 - 2087. [Abstract] [PDF]
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H. Dassule, P Lewis, M Bei, R Maas, and A. McMahon Sonic hedgehog regulates growth and morphogenesis of the tooth Development, January 11, 2000; 127(22): 4775 - 4785. [Abstract] [PDF]
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P Aza-Blanc, H. Lin, A Ruiz i Altaba, and T. Kornberg Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities Development, January 10, 2000; 127(19): 4293 - 4301. [Abstract] [PDF]
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R Brewster, J. Mullor, and A Ruiz i Altaba Gli2 functions in FGF signaling during antero-posterior patterning Development, January 10, 2000; 127(20): 4395 - 4405. [Abstract] [PDF]
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H. Park, C Bai, K. Platt, M. Matise, A Beeghly, C. Hui, M Nakashima, and A. Joyner Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation Development, January 4, 2000; 127(8): 1593 - 1605. [Abstract] [PDF]
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S. Baur, J. Mai, and S. Dymecki Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity Development, January 2, 2000; 127(3): 605 - 619. [Abstract] [PDF]
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K. Mizugishi, J. Aruga, K. Nakata, and K. Mikoshiba Molecular Properties of Zic Proteins as Transcriptional Regulators and Their Relationship to GLI Proteins J. Biol. Chem., January 12, 2001; 276(3): 2180 - 2188. [Abstract] [Full Text] [PDF]
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X.-Q. Wang and J. A Rothnagel Post-transcriptional Regulation of the GLI1 Oncogene by the Expression of Alternative 5' Untranslated Regions J. Biol. Chem., January 5, 2001; 276(2): 1311 - 1316. [Abstract] [Full Text] [PDF]
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