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Development, Vol 125, Issue 15 2759-2770, Copyright © 1998 by Company of Biologists


JOURNAL ARTICLES

Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system

MP Matise, DJ Epstein, HL Park, KA Platt and AL Joyner
Developmental Genetics Program and Howard Hughes Medical Institute, and Department of Cell Biology and Physiology and Neuroscience, NYU Medical Center, New York, NY 10016, USA.

Induction of the floor plate at the ventral midline of the neural tube is one of the earliest events in the establishment of dorsoventral (d/v) polarity in the vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog, has been shown to be both necessary and sufficient for this induction. In vertebrates, several downstream components of this signalling pathway have been identified, including members of the Gli transcription factor family. In this study, we have examined d/v patterning of the CNS in Gli2 mouse mutants. We have found that the floor plate throughout the midbrain, hindbrain and spinal cord does not form in Gli2 homozygotes. Despite this, motoneurons and ventral interneurons form in their normal d/v positions at 9.5 to 12.5 days postcoitum (dpc). However, cells that are generated in the region flanking the floor plate, including dopaminergic and serotonergic neurons, were greatly reduced in number or absent in Gli2 homozygous embryos. These results suggest that early signals derived from the notochord can be sufficient for establishing the basic d/v domains of cell differentiation in the ventral spinal cord and hindbrain. Interestingly, the notochord in Gli2 mutants does not regress ventrally after 10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-finger-deletion double homozygous mutants appeared similar to Gli2 homozygotes, indicating that neither gene is required downstream of Shh for the early development of ventral cell fates outside the ventral midline.
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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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JNCI J Natl Cancer InstHome page
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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DevelopmentHome page
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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DevelopmentHome page
E Lamar, C Kintner, and M Goulding
Identification of NKL, a novel Gli-Kruppel zinc-finger protein that promotes neuronal differentiation
Development, January 4, 2001; 128(8): 1335 - 1346.
[Abstract] [PDF]


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Genes Dev.Home page
A. P. McMahon
Neural patterning: The role of Nkx genes in the ventral spinal cord
Genes & Dev., September 15, 2000; 14(18): 2261 - 2264.
[Full Text]


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DevelopmentHome page
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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Hum Mol GenetHome page
P. Blader and U. Strahle
Zebrafish developmental genetics and central nervous system development
Hum. Mol. Genet., April 1, 2000; 9(6): 945 - 951.
[Abstract] [Full Text] [PDF]


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Physiol. Rev.Home page
J. C. Glover
Development of Specific Connectivity Between Premotor Neurons and Motoneurons in the Brain Stem and Spinal Cord
Physiol Rev, April 1, 2000; 80(2): 615 - 647.
[Abstract] [Full Text] [PDF]


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DevelopmentHome page
D. Epstein, L Martinu, J. Michaud, K. Losos, C Fan, and A. Joyner
Members of the bHLH-PAS family regulate Shh transcription in forebrain regions of the mouse CNS
Development, January 11, 2000; 127(21): 4701 - 4709.
[Abstract] [PDF]


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DevelopmentHome page
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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DevelopmentHome page
F Muller, S Albert, P Blader, N Fischer, M Hallonet, and U Strahle
Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS
Development, January 9, 2000; 127(18): 3889 - 3897.
[Abstract] [PDF]


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DevelopmentHome page
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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J. Neurosci.Home page
T. Hendricks, N. Francis, D. Fyodorov, and E. S. Deneris
The ETS Domain Factor Pet-1 Is an Early and Precise Marker of Central Serotonin Neurons and Interacts with a Conserved Element in Serotonergic Genes
J. Neurosci., December 1, 1999; 19(23): 10348 - 10356.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
G. Wang, B. Wang, and J. Jiang
Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus
Genes & Dev., November 1, 1999; 13(21): 2828 - 2837.
[Abstract] [Full Text]


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Cereb CortexHome page
J. L.R. Rubenstein, S. Anderson, L. Shi, E. Miyashita-Lin, A. Bulfone, and R. Hevner
Genetic Control of Cortical Regionalization and Connectivity
Cereb Cortex, September 1, 1999; 9(6): 524 - 532.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
P. Dai, H. Akimaru, Y. Tanaka, T. Maekawa, M. Nakafuku, and S. Ishii
Sonic Hedgehog-induced Activation of the Gli1 Promoter Is Mediated by GLI3
J. Biol. Chem., March 19, 1999; 274(12): 8143 - 8152.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
R. O. Karlstrom, W. S. Talbot, and A. F. Schier
Comparative synteny cloning of zebrafish you-too: mutations in the Hedgehog target gli2 affect ventral forebrain patterning
Genes & Dev., February 15, 1999; 13(4): 388 - 393.
[Abstract] [Full Text]


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J. Cell Sci.Home page
D. Stone, M Murone, S Luoh, W Ye, M. Armanini, A Gurney, H Phillips, J Brush, A Goddard, F. de Sauvage, et al.
Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli
J. Cell Sci., January 12, 1999; 112(23): 4437 - 4448.
[Abstract] [PDF]


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DevelopmentHome page
H Sasaki, Y Nishizaki, C Hui, M Nakafuku, and H Kondoh
Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling
Development, January 9, 1999; 126(17): 3915 - 3924.
[Abstract] [PDF]


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DevelopmentHome page
A. Borycki, B Brunk, S Tajbakhsh, M Buckingham, C Chiang, and C. Emerson
Sonic hedgehog controls epaxial muscle determination through Myf5 activation
Development, January 9, 1999; 126(18): 4053 - 4063.
[Abstract] [PDF]


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DevelopmentHome page
L Sussel, O Marin, S Kimura, and J. Rubenstein
Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum
Development, January 8, 1999; 126(15): 3359 - 3370.
[Abstract] [PDF]


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DevelopmentHome page
T Theil, G Alvarez-Bolado, A Walter, and U Ruther
Gli3 is required for Emx gene expression during dorsal telencephalon development
Development, January 8, 1999; 126(16): 3561 - 3571.
[Abstract] [PDF]


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DevelopmentHome page
M. Matise, M Lustig, T Sakurai, M Grumet, and A. Joyner
Ventral midline cells are required for the local control of commissural axon guidance in the mouse spinal cord
Development, January 8, 1999; 126(16): 3649 - 3659.
[Abstract] [PDF]


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DevelopmentHome page
D Arendt and K Nubler-Jung
Comparison of early nerve cord development in insects and vertebrates
Development, January 6, 1999; 126(11): 2309 - 2325.
[Abstract] [PDF]


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DevelopmentHome page
K. Lewis, G Drossopoulou, I. Paton, D. Morrice, K. Robertson, D. Burt, P. Ingham, and C Tickle
Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway
Development, January 6, 1999; 126(11): 2397 - 2407.
[Abstract] [PDF]


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DevelopmentHome page
A Ruiz i Altaba
Gli proteins encode context-dependent positive and negative functions: implications for development and disease
Development, January 6, 1999; 126(14): 3205 - 3216.
[Abstract] [PDF]


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DevelopmentHome page
F Muller, B Chang, S Albert, N Fischer, L Tora, and U Strahle
Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord
Development, January 5, 1999; 126(10): 2103 - 2116.
[Abstract] [PDF]


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DevelopmentHome page
D. Epstein, A. McMahon, and A. Joyner
Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanisms
Development, January 1, 1999; 126(2): 281 - 292.
[Abstract] [PDF]


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J. Biol. Chem.Home page
Y. Koyabu, K. Nakata, K. Mizugishi, J. Aruga, and K. Mikoshiba
Physical and Functional Interactions between Zic and Gli Proteins
J. Biol. Chem., March 2, 2001; 276(10): 6889 - 6892.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
M. Nilsson, A. B. Unden, D. Krause, U. Malmqwist, K. Raza, P. G. Zaphiropoulos, and R. Toftgard
Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1
PNAS, March 28, 2000; 97(7): 3438 - 3443.
[Abstract] [Full Text] [PDF]




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