|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
1 Department of Cell Biology, Duke University Medical Center, Durham, NC
27710-3709, USA
2 Victor Goodhill Ear Center, Head and Neck Surgery Division, University of
California, Los Angeles, CA 90095-1794, USA
* Author for correspondence (e-mail: kling{at}cellbio.duke.edu)
Accepted 23 July 2002
In this study we investigate the roles of the organizer factors chordin and noggin, which are dedicated antagonists of the bone morphogenetic proteins (BMPs), in formation of the mammalian head. The mouse chordin and noggin genes (Chrd and Nog) are expressed in the organizer (the node) and its mesendodermal derivatives, including the prechordal plate, an organizing center for rostral development. They are also expressed at lower levels in and around the anterior neural ridge, another rostral organizing center. To elucidate roles of Chrd and Nog that are masked by the severe phenotype and early lethality of the double null, we have characterized embryos of the genotype Chrd-/-;Nog+/-. These animals display partially penetrant neonatal lethality, with defects restricted to the head. The variable phenotypes include cyclopia, holoprosencephaly, and rostral truncations of the brain and craniofacial skeleton. In situ hybridization reveals a loss of SHH expression and signaling by the prechordal plate, and a decrease in FGF8 expression and signaling by the anterior neural ridge at the five-somite stage. Defective Chrd-/-;Nog+/- embryos exhibit reduced cell proliferation in the rostral neuroepithelium at 10 somites, followed by increased cell death 1 day later. Because these phenotypes result from reduced levels of BMP antagonists, we hypothesized that they are due to increased BMP activity. Ectopic application of BMP2 to wild-type cephalic explants results in decreased FGF8 and SHH expression in rostral tissue, suggesting that the decreased expression of FGF8 and SHH observed in vivo is due to ectopic BMP activity. Cephalic explants isolated from Chrd;Nog double mutant embryos show an increased sensitivity to ectopic BMP protein, further supporting the hypothesis that these mutants are deficient in BMP antagonism. These results indicate that the BMP antagonists chordin and noggin promote the inductive and trophic activities of rostral organizing centers in early development of the mammalian head.
Key words: Chordin, Noggin, BMP, Holoprosencephaly, Prechordal plate, Forebrain, Mouse
This article has been cited by other articles:
|
|
 |
|
  N. Mine, R. M. Anderson, and J. Klingensmith BMP antagonism is required in both the node and lateral plate mesoderm for mammalian left-right axis establishment Development, July 15, 2008; 135(14): 2425 - 2434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fernandes, G. Gutin, H. Alcorn, S. K. McConnell, and J. M. Hebert Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly Development, November 1, 2007; 134(21): 3789 - 3794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chen, G. Liao, L. Yang, K. Campbell, M. Nakafuku, C.-Y. Kuan, and Y. Zheng Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly PNAS, October 31, 2006; 103(44): 16520 - 16525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. v. d. Zee, O. Stockhammer, C. v. Levetzow, R. N. d. Fonseca, and S. Roth Sog/Chordin is required for ventral-to-dorsal Dpp/BMP transport and head formation in a short germ insect PNAS, October 31, 2006; 103(44): 16307 - 16312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lamba, M. O. Karl, C. B. Ware, and T. A. Reh Efficient generation of retinal progenitor cells from human embryonic stem cells PNAS, August 22, 2006; 103(34): 12769 - 12774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cheng, C.-m. Hsu, D. S. Currle, J. S. Hu, A. J. Barkovich, and E. S. Monuki Central roles of the roof plate in telencephalic development and holoprosencephaly. J. Neurosci., July 19, 2006; 26(29): 7640 - 7649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Storm, S. Garel, U. Borello, J. M. Hebert, S. Martinez, S. K. McConnell, G. R. Martin, and J. L. R. Rubenstein Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers Development, May 1, 2006; 133(9): 1831 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. ABE Function of BMPs and BMP Antagonists in Adult Bone Ann. N.Y. Acad. Sci., April 1, 2006; 1068(1): 41 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sur and J. L. R. Rubenstein Patterning and Plasticity of the Cerebral Cortex Science, November 4, 2005; 310(5749): 805 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hester, J. C. Thompson, J. Mills, Y. Liu, H. M. El-Hodiri, and M. Weinstein Smad1 and Smad8 Function Similarly in Mammalian Central Nervous System Development Mol. Cell. Biol., June 1, 2005; 25(11): 4683 - 4692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Spoelgen, A. Hammes, U. Anzenberger, D. Zechner, O. M. Andersen, B. Jerchow, and T. E. Willnow LRP2/megalin is required for patterning of the ventral telencephalon Development, January 15, 2005; 132(2): 405 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shimogori, V. Banuchi, H. Y. Ng, J. B. Strauss, and E. A. Grove Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex Development, November 15, 2004; 131(22): 5639 - 5647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zakin and E. M. De Robertis Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development Development, January 15, 2004; 131(2): 413 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schlombs, T. Wagner, and J. Scheel Site-1 protease is required for cartilage development in zebrafish PNAS, November 25, 2003; 100(24): 14024 - 14029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gulacsi and L. Lillien Sonic Hedgehog and Bone Morphogenetic Protein Regulate Interneuron Development from Dorsal Telencephalic Progenitors In Vitro J. Neurosci., October 29, 2003; 23(30): 9862 - 9872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. del Barco Barrantes, G. Davidson, H.-J. Grone, H. Westphal, and C. Niehrs Dkk1 and noggin cooperate in mammalian head induction Genes & Dev., September 15, 2003; 17(18): 2239 - 2244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bach, Y. Lallemand, M.-A. Nicola, C. Ramos, L. Mathis, M. Maufras, and B. Robert Msx1 is required for dorsal diencephalon patterning Development, September 1, 2003; 130(17): 4025 - 4036. [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]
|
|
