|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
doi: 10.1242/10.1242/dev.00364
1 Department of Biology, University of Massachusetts, Amherst, MA 01003,
USA
2 Developmental Genetics Program, Skirball Institute of Biomolecular Medicine
and Department of Cell Biology, New York University School of Medicine, New
York, NY 10016, USA
3 Department of Biological Science, University of Tokyo, Tokyo, Japan
4 Laboratory for Embryonic Induction, Center for Developmental Biology, RIKEN,
Kobe, 650-0047 Japan
5 Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871,
Japan
6 Department of Developmental Biology, Stanford University School of Medicine,
Stanford, CA 94305, USA
* Author for correspondence (e-mail: karlstrom{at}bio.umass.edu)
Accepted 14 November 2002
Gli proteins regulate the transcription of Hedgehog (Hh) target genes. Genetic studies in mouse have shown that Gli1 is not essential for embryogenesis, whereas Gli2 acts as an activator of Hh target genes. In contrast, misexpression studies in Xenopus and cultured cells have suggested that Gli1 can act as an activator of Hh-regulated genes, whereas Gli2 might function as a repressor of a subset of Hh targets. To clarify the roles of gli genes during vertebrate development, we have analyzed the requirements for gli1 and gli2 during zebrafish embryogenesis. We report that detour (dtr) mutations encode loss-of-function alleles of gli1. In contrast to mouse Gli1 mutants, dtr mutants and embryos injected with gli1 antisense morpholino oligonucleotides display defects in the activation of Hh target genes in the ventral neuroectoderm. Mutations in you-too (yot) encode C-terminally truncated Gli2. We find that these truncated proteins act as dominant repressors of Hh signaling, in part by blocking Gli1 function. In contrast, blocking Gli2 function by eliminating full-length Gli2 results in minor Hh signaling defects and uncovers a repressor function of Gli2 in the telencephalon. In addition, we find that Gli1 and Gli2 have activator functions during somite and neural development. These results reveal divergent requirements for Gli1 and Gli2 in mouse and zebrafish and indicate that zebrafish Gli1 is an activator of Hh-regulated genes, while zebrafish Gli2 has minor roles as a repressor or activator of Hh targets.
Key words: Forebrain patterning, Hedgehog signaling, Adaxial cells, floor plate, cyclopamine, Morpholino
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  J. Ninkovic, C. Stigloher, C. Lillesaar, and L. Bally-Cuif Gsk3{beta}/PKA and Gli1 regulate the maintenance of neural progenitors at the midbrain-hindbrain boundary in concert with E(Spl) factor activity Development, September 15, 2008; 135(18): 3137 - 3148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Guner, A. T. Ozacar, J. E. Thomas, and R. O. Karlstrom Graded Hedgehog and Fibroblast Growth Factor Signaling Independently Regulate Pituitary Cell Fates and Help Establish the Pars Distalis and Pars Intermedia of the Zebrafish Adenohypophysis Endocrinology, September 1, 2008; 149(9): 4435 - 4451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Eichberger, A. Kaser, C. Pixner, C. Schmid, S. Klingler, M. Winklmayr, C. Hauser-Kronberger, F. Aberger, and A.-M. Frischauf GLI2-specific Transcriptional Activation of the Bone Morphogenetic Protein/Activin Antagonist Follistatin in Human Epidermal Cells J. Biol. Chem., May 2, 2008; 283(18): 12426 - 12437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Galvin, H. Ye, D. J. Erstad, R. Feddersen, and C. Wetmore Gli1 Induces G2/M Arrest and Apoptosis in Hippocampal but Not Tumor-Derived Neural Stem Cells Stem Cells, April 1, 2008; 26(4): 1027 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Bar, A. Chaudhry, A. Lin, X. Fan, K. Schreck, W. Matsui, S. Piccirillo, A. L. Vescovi, F. DiMeco, A. Olivi, et al. Cyclopamine-Mediated Hedgehog Pathway Inhibition Depletes Stem-Like Cancer Cells in Glioblastoma Stem Cells, October 1, 2007; 25(10): 2524 - 2533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, B. P. Srinivas, S. Y. Tay, A. Mak, X. Yu, S. G. P. Lee, H. Yang, K. R. Govindarajan, B. Leong, G. Bourque, et al. Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development Genetics, October 1, 2006; 174(2): 735 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pan, C. B. Bai, A. L. Joyner, and B. Wang Sonic hedgehog Signaling Regulates Gli2 Transcriptional Activity by Suppressing Its Processing and Degradation. Mol. Cell. Biol., May 1, 2006; 26(9): 3365 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Seth, J. Culverwell, M. Walkowicz, S. Toro, J. M. Rick, S. C. F. Neuhauss, Z. M. Varga, and R. O. Karlstrom belladonna/(lhx2) is required for neural patterning and midline axon guidance in the zebrafish forebrain Development, February 15, 2006; 133(4): 725 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. F. Barresi, L. D. Hutson, C.-B. Chien, and R. O. Karlstrom Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain Development, August 15, 2005; 132(16): 3643 - 3656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Roessler, A. N. Ermilov, D. K. Grange, A. Wang, M. Grachtchouk, A. A. Dlugosz, and M. Muenke A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2 Hum. Mol. Genet., August 1, 2005; 14(15): 2181 - 2188. [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]
|
|
|
|
|
|
I. Masai, M. Yamaguchi, N. Tonou-Fujimori, A. Komori, and H. Okamoto The hedgehog-PKA pathway regulates two distinct steps of the differentiation of retinal ganglion cells: the cell-cycle exit of retinoblasts and their neuronal maturation Development, April 1, 2005; 132(7): 1539 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Stamataki, F. Ulloa, S. V. Tsoni, A. Mynett, and J. Briscoe A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube Genes & Dev., March 1, 2005; 19(5): 626 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Tay, P. W. Ingham, and S. Roy A homologue of the Drosophila kinesin-like protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo Development, February 15, 2005; 132(4): 625 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Feng, B. White, O. V. Tyurina, B. Guner, T. Larson, H. Y. Lee, R. O. Karlstrom, and J. D. Kohtz Synergistic and antagonistic roles of the Sonic hedgehog N- and C-terminal lipids Development, September 1, 2004; 131(17): 4357 - 4370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wolff, S. Roy, K. E. Lewis, H. Schauerte, G. Joerg-Rauch, A. Kirn, C. Weiler, R. Geisler, P. Haffter, and P. W. Ingham iguana encodes a novel zinc-finger protein with coiled-coil domains essential for Hedgehog signal transduction in the zebrafish embryo Genes & Dev., July 1, 2004; 18(13): 1565 - 1576. [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]
|
|
|
|
|
|
K. E. Lewis and J. S. Eisen Paraxial mesoderm specifies zebrafish primary motoneuron subtype identity Development, February 15, 2004; 131(4): 891 - 902. [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]
|
|
|
|
|
|
J. M. Ungos, R. O. Karlstrom, and D. W. Raible Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons Development, November 15, 2003; 130(22): 5351 - 5362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Roessler, Y.-Z. Du, J. L. Mullor, E. Casas, W. P. Allen, G. Gillessen-Kaesbach, E. R. Roeder, J. E. Ming, A. R. i Altaba, and M. Muenke Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features PNAS, November 11, 2003; 100(23): 13424 - 13429. [Abstract] [Full Text] [PDF]
|
|
