Development, Vol 124, Issue 13 2537-2552, Copyright © 1997 by Company of Biologists

JOURNAL ARTICLES

Gli1 is a target of Sonic hedgehog that induces ventral neural tube development

J Lee, KA Platt, P Censullo and A Ruiz i Altaba
The Skirball Institute, Developmental Genetics Program and Department of Cell Biology, NYU Medical Center, New York, NY 10016, USA.

The vertebrate zinc finger genes of the Gli family are homologs of the Drosophila gene cubitus interruptus. In frog embryos, Gli1 is expressed transiently in the prospective floor plate during gastrulation and in cells lateral to the midline during late gastrula and neurula stages. In contrast, Gli2 and Gli3 are absent from the neural plate midline with Gli2 expressed widely and Gli3 in a graded fashion with highest levels in lateral regions. In mouse embryos, the three Gli genes show a similar pattern of expression in the neural tube but are coexpressed throughout the early neural plate. Because Gli1 is the only Gli gene expressed in prospective floor plate cells of frog embryos, we have investigated a possible involvement of this gene in ventral neural tube development. Here we show that Shh signaling activates Gli1 transcription and that widespread expression of endogenous frog or human glioma Gli1, but not Gli3, in developing frog embryos results in the ectopic differentiation of floor plate cells and ventral neurons within the neural tube. Floor-plate-inducing ability is retained when cytoplasmic Gli1 proteins are forced into the nucleus or are fused to the VP16 transactivating domain. Thus, our results identify Gli1 as a midline target of Shh and suggest that it mediates the induction of floor plate cells and ventral neurons by Shh acting as a transcriptional regulator.
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				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]

				N Dahmane and A Ruiz-i-Altaba Sonic hedgehog regulates the growth and patterning of the cerebellum Development, January 6, 1999; 126(14): 3089 - 3100. [Abstract] [PDF]

				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]

				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]

				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]

				J. A. Waschek, R. A. Casillas, T. B. Nguyen, E. M. DiCicco-Bloom, E. M. Carpenter, and W. I. Rodriguez Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: Potential role in patterning and neurogenesis PNAS, August 4, 1998; 95(16): 9602 - 9607. [Abstract] [Full Text] [PDF]

				S. Yang, A. Lockwood, P. Hollett, R. Ford, and K. Kao Overexpression of a Novel Xenopus Rel mRNA Gene Induces Tumors in Early Embryos J. Biol. Chem., May 29, 1998; 273(22): 13746 - 13752. [Abstract] [Full Text] [PDF]

				J. Kohtz, D. Baker, G Corte, and G Fishell Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog Development, January 12, 1998; 125(24): 5079 - 5089. [Abstract] [PDF]

				M. Matise, D. Epstein, H. Park, K. Platt, and A. Joyner Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system Development, January 8, 1998; 125(15): 2759 - 2770. [Abstract] [PDF]

				Z Hardcastle, R Mo, C. Hui, and P. Sharpe The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants Development, January 8, 1998; 125(15): 2803 - 2811. [Abstract] [PDF]

				Q Ding, J Motoyama, S Gasca, R Mo, H Sasaki, J Rossant, and C. Hui Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice Development, January 7, 1998; 125(14): 2533 - 2543. [Abstract] [PDF]

				A Ruiz i Altaba Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog Development, January 6, 1998; 125(12): 2203 - 2212. [Abstract] [PDF]

				E. Grove, S Tole, J Limon, L Yip, and C. Ragsdale The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice Development, January 6, 1998; 125(12): 2315 - 2325. [Abstract] [PDF]

				C Hayes, J. Brown, M. Lyon, and G. Morriss-Kay Sonic hedgehog is not required for polarising activity in the Doublefoot mutant mouse limb bud Development, January 2, 1998; 125(3): 351 - 357. [Abstract] [PDF]

				A. Borycki, L Mendham, and C. Emerson Control of somite patterning by Sonic hedgehog and its downstream signal response genes Development, January 2, 1998; 125(4): 777 - 790. [Abstract] [PDF]