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Science 22 August 1997:
Vol. 277. no. 5329, pp. 1109 - 1113
DOI: 10.1126/science.277.5329.1109
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Reports

Altered Neural Cell Fates and Medulloblastoma in Mouse patched Mutants

Lisa V. Goodrich, Ljiljana Milenkovic, Kay M. Higgins, Matthew P. Scott *

The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS). Functions of PTC were investigated by inactivating the mouse gene. Mice homozygous for the ptc mutation died during embryogenesis and were found to have open and overgrown neural tubes. Two Shh target genes, ptc itself and Gli, were derepressed in the ectoderm and mesoderm but not in the endoderm. Shh targets that are, under normal conditions, transcribed ventrally were aberrantly expressed in dorsal and lateral neural tube cells. Thus Ptc appears to be essential for repression of genes that are locally activated by Shh. Mice heterozygous for the ptc mutation were larger than normal, and a subset of them developed hindlimb defects or cerebellar medulloblastomas, abnormalities also seen in BCNS patients.

Departments of Developmental Biology and Genetics and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5427, USA.
*   To whom correspondence should be addressed. E-mail: scott{at}cmgm.stanford.edu

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The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation.
J. D. Corrales, S. Blaess, E. M. Mahoney, and A. L. Joyner (2006)
Development 133, 1811-1821
   Abstract »    Full Text »    PDF »
Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies..
K. Sasai, J. T. Romer, Y. Lee, D. Finkelstein, C. Fuller, P. J. McKinnon, and T. Curran (2006)
Cancer Res. 66, 4215-4222
   Abstract »    Full Text »    PDF »
Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis.
J. K. Sicklick, Y.-X. Li, A. Jayaraman, R. Kannangai, Y. Qi, P. Vivekanandan, J. W. Ludlow, K. Owzar, W. Chen, M. S. Torbenson, et al. (2006)
Carcinogenesis 27, 748-757
   Abstract »    Full Text »    PDF »
N-myc Can Substitute for Insulin-Like Growth Factor Signaling in a Mouse Model of Sonic Hedgehog-Induced Medulloblastoma..
S. R. Browd, A. M. Kenney, O. N. Gottfried, J. W. Yoon, D. Walterhouse, C. A. Pedone, and D. W. Fults (2006)
Cancer Res. 66, 2666-2672
   Abstract »    Full Text »    PDF »
Patched1 Functions as a Gatekeeper by Promoting Cell Cycle Progression.
C. Adolphe, R. Hetherington, T. Ellis, and B. Wainwright (2006)
Cancer Res. 66, 2081-2088
   Abstract »    Full Text »    PDF »
The Sonic hedgehog pathway independently controls the patterning, proliferation and survival of neuroepithelial cells by regulating Gli activity.
J. Cayuso, F. Ulloa, B. Cox, J. Briscoe, and E. Marti (2006)
Development 133, 517-528
   Abstract »    Full Text »    PDF »
Defective cerebellar response to mitogenic Hedgehog signaling in Down's syndrome mice.
R. J. Roper, L. L. Baxter, N. G. Saran, D. K. Klinedinst, P. A. Beachy, and R. H. Reeves (2006)
PNAS 103, 1452-1456
   Abstract »    Full Text »    PDF »
Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates.
D. Huangfu and K. V. Anderson (2006)
Development 133, 3-14
   Abstract »    Full Text »    PDF »
Tectonic, a novel regulator of the Hedgehog pathway required for both activation and inhibition.
J. F. Reiter and W. C. Skarnes (2006)
Genes & Dev. 20, 22-27
   Abstract »    Full Text »    PDF »
The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation.
T. Uziel, F. Zindy, S. Xie, Y. Lee, A. Forget, S. Magdaleno, J. E. Rehg, C. Calabrese, D. Solecki, C. G. Eberhart, et al. (2005)
Genes & Dev. 19, 2656-2667
   Abstract »    Full Text »    PDF »
Splitting the Hedgehog signal: sex and patterning in Drosophila.
J. I. Horabin (2005)
Development 132, 4801-4810
   Abstract »    Full Text »    PDF »
Cardiac and CNS defects in a mouse with targeted disruption of suppressor of fused.
A. F. Cooper, K. P. Yu, M. Brueckner, L. L. Brailey, L. Johnson, J. M. McGrath, and A. E. Bale (2005)
Development 132, 4407-4417
   Abstract »    Full Text »    PDF »


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