Crossref journal-article
The Company of Biologists
Development (237)
Abstract

ABSTRACT Within the developing vertebrate nervous system, it is not known how progenitor cells interpret the positional information provided by inducing signals or how the domains in which distinct groups of neural cells differentiate are defined. Gli proteins may be involved in these processes. In the frog neural plate, we have previously shown that the zinc finger transcription factor Gli1 is expressed in midline cells and mediates the effects of Shh inducing floor plate differentiation. In contrast, Gli2 and Gli3 are expressed throughout the neural plate except for the midline. Here, it is shown that Gli3 and Shh repress each other whereas Gli2, like Gli1, is a target of Shh signaling. However, only Gli1 can induce the differentiation of floor plate cells. In addition, Gli2 and Gli3 repress the ectopic induction of floor plate cells by Gli1 in co-injection assays and inhibit endogenous floor plate differentiation. The definition of the floor plate domain, therefore, appears to be defined by the antagonizing activities of Gli2 and Gli3 on Gli1 function. Because both Gli1 and Gli2 are induced by Shh, these results establish a regulatory feedback loop triggered by Shh that restricts floor plate cells to the midline. We have also previously shown that the Gli genes induce neuronal differentiation and here it is shown that there is specificity to the types of neurons the Gli proteins induce. Only Gli1 induces Nkx2.1/TTF-1+ ventral forebrain neurons. Moreover, Gli2 and Gli3 inhibit their differentiation. In contrast, the differentiation of spinal motor neurons can be induced by the two ventrally expressed Gli genes, Gli1 and Gli2, suggesting that Gli2 directly mediates induction of motor neurons by Shh. In addition, Gli3 inhibits motor neuron differentiation by Gli2. Thus, combinatorial Gli function may pattern the neural tube, integrating positional information and cell type differentiation.

Bibliography

Altaba, A. R. i. (1998). Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development, 125(12), 2203–2212.

Authors 1
  1. A. Ruiz i Altaba (first)
References 59 Referenced 191
  1. 10.1016/S0092-8674(00)80292-5 / Cell / Proteolysis that is inhibited by Hedgehog targets Cubitus Interruptus protein to the nucleus and converts it to a represor by Aza-Blanc (1997)
  2. 10.1038/31242 / Nature, in press / Gli/Zic factors pattern the neural plate by defining domains of cell differentiation by Brewster (1998)
  3. 10.1016/S0925-4773(97)00656-4 / Mech. Dev / Evidence for genetic control of Sonic hedgehog by Gli3 in mouse limb development by Büscher (1997)
  4. 10.1038/383407a0 / Nature / Cyclopia and defective axial patterning in mice lackingSonic hedgehog gene function by Chiang (1996)
  5. 10.1242/dev.121.7.2099 / Development / Dorsalization of the neural tube by the non-neural ectoderm by Dickinson (1995)
  6. 10.1101/gad.4.6.1068 / Genes Dev / Repression of ci-D in posterior compartments of Drosophila by engrailed by Eaton (1990)
  7. 10.1016/0092-8674(93)90627-3 / Cell / Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity by Echelard (1993)
  8. 10.1242/dev.121.8.2337 / Development / Distinct expression and shared activities of members of the hdgehog gene family of Xenopus laevis by Ekker (1995)
  9. 10.1016/0092-8674(95)90536-7 / Cell / Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube by Ericson (1995)
  10. 10.1016/S0092-8674(00)81386-0 / Cell / Two critical periods of Sonic hedgehog signaling required for the specification of motor neuron identity by Eriscon (1996)
  11. 10.1159/000147600 / Acta Anat / Extra-toes (Xt) homozygous mutant mice demonstrate a role of the Gli-3 gene in the development of the forebrain by Franz (1994)
  12. {'key': '2025021501152859000_DEVELOP_125_12_2203C12', 'first-page': '675', 'article-title': 'In situ hybridization: an improved whole mount method for Xenopus embryos', 'volume': '36', 'author': 'Harland', 'year': '1991', 'journal-title': 'Meth. Enzymol'} / Meth. Enzymol / In situ hybridization: an improved whole mount method for Xenopus embryos by Harland (1991)
  13. 10.1101/gad.12.2.186 / Genes Dev / Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor by Hata (1998)
  14. 10.1016/S0092-8674(00)80303-7 / Cell / The MAD-related protein Smad7 associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling by Hayashi (1997)
  15. 10.1006/geno.1996.4468 / Genomics / Cloning and sequencing of the mouse Gli2 gene: localization to the Dominant hemimelia critical region by Hughes (1997)
  16. 10.1038/ng0393-241 / Nature Genetics / A mouse model of Greig cephalopolysyndatyly syndrome: the extra-toes mutation contains an intragenic deletion of the Gli3 gene by Hui (1993)
  17. 10.1006/dbio.1994.1097 / Dev. Biol / Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm and mesoderm-derived tissues suggests multiple roles during postimplantation development by Hui (1994)
  18. 10.1016/0896-6273(95)90062-4 / Neuron / Induction of midbrain dopaminergic neurons by sonic hedgehog by Hynes (1995)
  19. 10.1016/S0896-6273(00)80344-X / Neuron / Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli1 by Hynes (1997)
  20. 10.1038/39355 / Nature / Smad6 inhibits signalling by the TGFβ superfamily by Imamura (1997)
  21. 10.1038/ng0397-266 / Nature Genetics / Gli3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome by Kang (1997)
  22. 10.1006/dbio.1997.8572 / Dev. Biol / XATH-1, a vertebrate homolog of Drosophila atonal, induces neuronal differentiation within ectodermal precursors by Kim (1997)
  23. 10.1126/science.3563490 / Science / Identification of an amplified, highly expressed gene in a human glioma by Kinzler (1987)
  24. {'key': '2025021501152859000_DEVELOP_125_12_2203C24', 'first-page': '634', 'article-title': 'The GLI gene encodes a nuclear protein which binds specific sequences in the human genome', 'volume': '10', 'author': 'Kinzler', 'year': '1990', 'journal-title': 'Mol. Cell Biol'} / Mol. Cell Biol / The GLI gene encodes a nuclear protein which binds specific sequences in the human genome by Kinzler (1990)
  25. 10.1016/0092-8674(93)90628-4 / Cell / A functionally conserved homolog of the Drosophila segment polarity gene hedgehog is expressed in tissues with polarizing activity in zebrafish embryos by Krauss (1993)
  26. 10.1242/dev.113.4.1093 / Development / The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the fetal brain by Lazzaro (1991)
  27. 10.1242/dev.124.13.2537 / Development / Gli1 is a target of sonic hedgehog that induces ventral neural tube development by Lee (1997)
  28. 10.1016/0092-8674(95)90276-7 / Cell / Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm by Liem (1995)
  29. 10.1006/dbio.1996.0300 / Dev. Biol / Sonic hedgehogdifferentially regulates expression of Gli and Gli3 during limb development by Marigo (1996)
  30. 10.1016/S0925-4773(97)00050-6 / Mech Dev / A role for Xenopus Gli-type zinc finger proteins in the early embryonic patterning of mesoderm and neuroectoderm by Marine (1997)
  31. 10.1038/375322a0 / Nature / Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants by Martí (1995)
  32. 10.1101/gad.9.13.1645 / Genes Dev / Duplicated zone of polarizing activity in polydactylous mouse mutants by Masuya (1995)
  33. 10.1242/dev.124.1.113 / Development / Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development by Mo (1997)
  34. 10.1016/0012-1606(89)90295-9 / Dev. Biol / Neural fold formation in newly created boundaries between neural plate and epidermis in the axolotl by Moury (1989)
  35. 10.1038/39369 / Nature / Identification of Smad7, a TGFβ-inducible antagonist of TGFβ signaling by Nakao (1997)
  36. {'volume-title': 'Normal Table of Xenopus laevis (Daudin)', 'year': '1967', 'author': 'Nieuwkoop', 'key': '2025021501152859000_DEVELOP_125_12_2203C36'} / Normal Table of Xenopus laevis (Daudin) by Nieuwkoop (1967)
  37. 10.1242/dev.118.2.563 / Development / Oligodendrocyte precursors originate at the ventral ventricular zone dorsal to the ventral midline regions in the embryonic rat spinal cord by Noll (1993)
  38. 10.1101/gad.4.6.1053 / Genes Dev / Cloning and characterization of the segment polarity gene cubitus interruptus dominant of Drosophila by Orenic (1990)
  39. 10.1126/science.8378770 / Science / Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers by Pavletich (1993)
  40. 10.1242/dev.117.1.205 / Development / Induction of floor plate differentiation by contact-dependent homeogenetic signals by Placzek (1993)
  41. {'key': '2025021501152859000_DEVELOP_125_12_2203C41', 'first-page': '121', 'article-title': 'Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of hedgehog signals suggesting a conservation of pathways between flies and mice', 'volume': '62', 'author': 'Platt', 'year': '1997', 'journal-title': 'Development'} / Development / Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of hedgehog signals suggesting a conservation of pathways between flies and mice by Platt (1997)
  42. {'key': '2025021501152859000_DEVELOP_125_12_2203C42', 'first-page': '401', 'article-title': 'Sonic hedgehog mediates the polarizing activity of the ZPA', 'volume': '751', 'author': 'Riddle', 'year': '1993', 'journal-title': 'Cell'} / Cell / Sonic hedgehog mediates the polarizing activity of the ZPA by Riddle (1993)
  43. 10.1016/0168-9525(96)10044-5 / Trends Genet / From gradients to stripes in Drosophila embryogenesis: filling in the gaps by Rivera-Pomar (1996)
  44. 10.1016/0092-8674(94)90514-2 / Cell / Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord by Roelink (1994)
  45. 10.1016/0092-8674(95)90397-6 / Cell / Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis by Roelink (1995)
  46. {'volume-title': 'In Essential Developmental Biology -A Practical Approach', 'year': '1993', 'author': 'Altaba', 'key': '2025021501152859000_DEVELOP_125_12_2203C46'} / In Essential Developmental Biology -A Practical Approach by Altaba (1993)
  47. 10.1016/S0092-8674(00)80325-6 / Cell / Catching a Gli-mpse of Hedgehog by Altaba (1997)
  48. 10.1006/mcne.1995.1011 / Mol. Cell. Neurosci / Restrictions to floor plate induction by hedgehog and winged helix genes in the neural tube of frog embryos by Ruiz i Altaba (1995)
  49. 10.1101/gad.8.11.1311 / Genes Dev / Xenopus embryos regulate nuclear localization of XmyoD by Rupp (1994)
  50. {'key': '2025021501152859000_DEVELOP_125_12_2203C50', 'first-page': '3104', 'article-title': 'The GLI-Kruppel family of human genes', 'volume': '8', 'author': 'Ruppert', 'year': '1988', 'journal-title': 'Mol. Cell. Biol'} / Mol. Cell. Biol / The GLI-Kruppel family of human genes by Ruppert (1988)
  51. {'key': '2025021501152859000_DEVELOP_125_12_2203C51', 'first-page': '5408', 'article-title': 'GLI3 encodes a 190 kilodalton protein with multiple regions of GLI similarity', 'volume': '10', 'author': 'Ruppert', 'year': '1990', 'journal-title': 'Mol. Cell Biol'} / Mol. Cell Biol / GLI3 encodes a 190 kilodalton protein with multiple regions of GLI similarity by Ruppert (1990)
  52. 10.1006/dbio.1997.8625 / Dev. Biol / Dorsal-ventral patterning during neural induction in Xenopus: Assessment of spinal cord regionalization with xHB9, a marker for the motor neuron reigion by Saha (1997)
  53. 10.1242/dev.124.7.1313 / Development / A binding site for Gli proteins is essential for HNF-3β floor plate enhancer activity in transgenics and can respond to Shh in vitro by Sasaki (1997)
  54. 10.1038/39362 / Nature / Daughters against dpp modulates dpp organizing activity in Drosophila wing development by Tsuneizumi (1997)
  55. 10.1101/gad.8.12.1434 / Genes Dev / Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate by Turner (1994)
  56. 10.1038/352539a0 / Nature / Gli3 zinc-finger gene interrupted by translocations in Greig syndrome families by Vortkamp (1991)
  57. 10.1089/dna.1995.14.629 / DNA Cell Biol / Identification of optimized target sequences for the GLI3 zinc finger protein by Vortkamp (1995)
  58. 10.1002/aja.1001960203 / Dev. Dyn / gli, a zinc finger transcription factor and oncogene, is expressed during normal mouse development by Walterhouse (1993)
  59. 10.1016/0896-6273(94)90450-2 / Neuron / Embryonic expression of myelin genes: evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube by Yu (1994)
Dates
Type When
Created 4 years, 4 months ago (April 26, 2021, 12:08 a.m.)
Deposited 6 months, 2 weeks ago (Feb. 14, 2025, 8:15 p.m.)
Indexed 3 weeks, 2 days ago (Aug. 6, 2025, 9:02 a.m.)
Issued 27 years, 2 months ago (June 15, 1998)
Published 27 years, 2 months ago (June 15, 1998)
Published Online 27 years, 2 months ago (June 15, 1998)
Published Print 27 years, 2 months ago (June 15, 1998)
Funders 0

None

@article{Altaba_1998, title={Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog}, volume={125}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.125.12.2203}, DOI={10.1242/dev.125.12.2203}, number={12}, journal={Development}, publisher={The Company of Biologists}, author={Altaba, A. Ruiz i}, year={1998}, month=jun, pages={2203–2212} }