|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 126, Issue 20 4431-4440, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
L Milenkovic, LV Goodrich, KM Higgins and MP Scott
Departments of Developmental Biology and Genetics, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California, USA.
Hedgehog (Hh) proteins control many developmental events by inducing specific cell fates or regulating cell proliferation. The Patched1 (Ptc1) protein, a binding protein for Hh molecules, appears to oppose Hh signals by repressing transcription of genes that can be activated by Hh. Sonic hedgehog (Shh), one of the vertebrate homologs of Hh, controls patterning and growth of the limb but the early embryonic lethality of ptc1(-)(/)(-) mice obscures the roles of ptc1 in later stages of development. We partially rescued ptc1 homozygous mutant embryos using a metallothionein promoter driving ptc1. In a wild-type background, the transgene causes a marked decrease in animal size starting during embryogenesis, and loss of anterior digits. In ptc1 homozygotes, a potent transgenic insert allowed survival to E14 and largely normal morphology except for midbrain overgrowth. A less potent transgene gave rise to partially rescued embryos with massive exencephaly, and polydactyly and branched digits in the limbs. The polydactyly was preceded by unexpected anterior limb bud transcription of Shh, so one function of ptc1 is to repress Shh expression in the anterior limb bud.
This article has been cited by other articles:
|
|
 |
|
  B. L. Allen, T. Tenzen, and A. P. McMahon The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development Genes & Dev., May 15, 2007; 21(10): 1244 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bok, D. K. Dolson, P. Hill, U. Ruther, D. J. Epstein, and D. K. Wu Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear Development, May 1, 2007; 134(9): 1713 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakatomi, I. Morita, K. Eto, and M.S. Ota Sonic Hedgehog Signaling is Important in Tooth Root Development. J. Dent. Res., May 1, 2006; 85(5): 427 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Horabin Splitting the Hedgehog signal: sex and patterning in Drosophila Development, November 1, 2005; 132(21): 4801 - 4810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N K Ragge, A Salt, J R O Collin, A Michalski, and P A Farndon Gorlin syndrome: the PTCH gene links ocular developmental defects and tumour formation Br. J. Ophthalmol., August 1, 2005; 89(8): 988 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Colnot, L. de la Fuente, S. Huang, D. Hu, C. Lu, B. St-Jacques, and J. A. Helms Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development Development, March 1, 2005; 132(5): 1057 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jeong and A. P. McMahon Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1 Development, January 1, 2005; 132(1): 143 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. V. Bulgakov, J. T. Eggenschwiler, D.-H. Hong, K. V. Anderson, and T. Li FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues Development, May 1, 2004; 131(9): 2149 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C.M. Black, C. J. Mazerolle, Y. Wang, K. D. Campsall, D. Petrin, B. C. Leonard, K. F. Damji, D. G. Evans, D. McLeod, and V. A. Wallace Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog signaling during retinal development Hum. Mol. Genet., December 15, 2003; 12(24): 3269 - 3276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Krebs, C. M. Schreiner, W. J. Scott Jr, S. M. Bell, D. J. Robbins, J. A. Goetz, H. Alt, N. Hawes, E. Wolf, and J. Favor Replicated anterior zeugopod (raz): a polydactylous mouse mutant with lowered Shh signaling in the limb bud Development, December 15, 2003; 130(24): 6037 - 6047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Gofflot, C. Hars, F. Illien, F. Chevy, C. Wolf, J. J. Picard, and C. Roux Molecular mechanisms underlying limb anomalies associated with cholesterol deficiency during gestation: implications of Hedgehog signaling Hum. Mol. Genet., May 15, 2003; 12(10): 1187 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Roessler and M. Muenke How a Hedgehog might see holoprosencephaly Hum. Mol. Genet., April 2, 2003; 12(90001): R15 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. McCarthy and W. S. Argraves Megalin and the neurodevelopmental biology of sonic hedgehog and retinol J. Cell Sci., March 15, 2003; 116(6): 955 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ybot-Gonzalez, P. Cogram, D. Gerrelli, and A. J. Copp Sonic hedgehog and the molecular regulation of mouse neural tube closure Development, March 7, 2003; 129(10): 2507 - 2517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-T. Chuang, T'N. Kawcak, and A. P. McMahon Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung Genes & Dev., February 1, 2003; 17(3): 342 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Bailey, L. Milenkovic, M. P. Scott, J. F. Collawn, and R. L. Johnson Several PATCHED1 Missense Mutations Display Activity in patched1-Deficient Fibroblasts J. Biol. Chem., September 6, 2002; 277(37): 33632 - 33640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Varghese, A. D. Gagliardi, P. E. Bialek, S.-P. Yee, G. F. Wagner, and G. E. Dimattia Overexpression of Human Stanniocalcin Affects Growth and Reproduction in Transgenic Mice Endocrinology, March 1, 2002; 143(3): 868 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Haraguchi, R. Mo, C.-c. Hui, J. Motoyama, S. Makino, T. Shiroishi, W. Gaffield, and G. Yamada Unique functions of Sonic hedgehog signaling during external genitalia development Development, November 1, 2001; 128(21): 4241 - 4250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Kim and M. Hebrok Intercellular signals regulating pancreas development and function Genes & Dev., January 15, 2001; 15(2): 111 - 127. [Full Text]
|
|
|
|
|
|
H. Dassule, P Lewis, M Bei, R Maas, and A. McMahon Sonic hedgehog regulates growth and morphogenesis of the tooth Development, January 11, 2000; 127(22): 4775 - 4785. [Abstract] [PDF]
|
|
|
|
|
|
G Drossopoulou, K. Lewis, J. Sanz-Ezquerro, N Nikbakht, A. McMahon, C Hofmann, and C Tickle A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling Development, January 4, 2000; 127(7): 1337 - 1348. [Abstract] [PDF]
|
|
