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Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm

Selleck, Mark A. J. and García-Castro, Martin I. and Artinger, Kristin B. and Bronner-Fraser, Marianne (1998) Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm. Development, 125 (24). pp. 4919-4930. ISSN 0950-1991.

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To define the timing of neural crest formation, we challenged the fate of presumptive neural crest cells by grafting notochords, Sonic Hedgehog- (Shh) or Noggin-secreting cells at different stages of neurulation in chick embryos. Notochords or Shh-secreting cells are able to prevent neural crest formation at open neural plate levels, as assayed by DiI-labeling and expression of the transcription factor, Slug, suggesting that neural crest cells are not committed to their fate at this time. In contrast, the BMP signaling antagonist, Noggin, does not repress neural crest formation at the open neural plate stage, but does so if injected into the lumen of the closing neural tube. The period of Noggin sensitivity corresponds to the time when BMPs are expressed in the dorsal neural tube but are down-regulated in the non-neural ectoderm. To confirm the timing of neural crest formation, Shh or Noggin were added to neural folds at defined times in culture. Shh inhibits neural crest production at early stages (0-5 hours in culture), whereas Noggin exerts an effect on neural crest production only later (5-10 hours in culture). Our results suggest three phases of neurulation that relate to neural crest formation: (1) an initial BMP-independent phase that can be prevented by Shh-mediated signals from the notochord; (2) an intermediate BMP-dependent phase around the time of neural tube closure, when BMP-4 is expressed in the dorsal neural tube; and (3) a later pre-migratory phase which is refractory to exogenous Shh and Noggin.

Item Type:Article
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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:Copyright © 1998 by Company of Biologist. Accepted 30 September; published on WWW 12 November 1998. We are indebted to Drs Clare Baker, Meyer Barembaum, Andy Groves, Robb Krumlauf and Carole LaBonne for helpful comments on the manuscript. Many of the reagents used in this study were the kind gifts from colleagues: Noggin-expressing CHO cells were provided by Dr Richard Harland, the Shh retrovirus by Dr Cliff Tabin, the BMP-4 probe used for in situ hybridization by Dr Paul Brickell, the Slug probe Dr Angela Nieto, the Pax-3 probe by Dr Michael Stark, and the Wnt-1 probe by Dr Mary Dickinson. Dr Christophe Marcelle generously assisted with preparation of some of the cells for injection. John Neri kindly helped with the paraffin sectioning and Nikki Pinkerton assisted with in situ hybridizations. M. A. J. S. and M. I. G.-C. performed the experiments reported in this manuscript, K. B. A. helped with the pilot studies and M. B.-F. provided assistance in writing the manuscript, intellectual input and help with cell grafts. M. A. J. S. was supported by a Markey research fellowship and M. I. G.-C. by the American Heart Association (no. 1140-FI1). This work was supported by USPHS NS34671, NS36585 and a grant from the March of Dimes Birth Defects Association.
Funding AgencyGrant Number
Lucille P. Markey Charitable TrustUNSPECIFIED
American Heart Association1140-FI1
U.S. Public Health Service (USPHS)NS34671
U.S. Public Health Service (USPHS)NS36585
March of Dimes Birth Defects AssociationUNSPECIFIED
Issue or Number:24
Record Number:CaltechAUTHORS:20090925-103910673
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Official Citation:MA Selleck, MI Garcia-Castro, KB Artinger, and M Bronner-Fraser Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm Development 125: 4919-4930.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:16057
Deposited By: George Porter
Deposited On:05 Oct 2009 16:18
Last Modified:03 Oct 2019 01:07

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