Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 297 (5582): 848-851

Copyright © 2002 by the American Association for the Advancement of Science

Ectodermal Wnt Function as a Neural Crest Inducer

Martín I. García-Castro,* Christophe Marcelle,dagger Marianne Bronner-Fraser

Neural crest cells, which generate peripheral nervous system and facial skeleton, arise at the neural plate/ectodermal border via an inductive interaction between these tissues. Wnts and bone morphogenetic proteins (BMPs) play roles in neural crest induction in amphibians and zebrafish. Here, we show that, in avians, Wnt6 is localized in ectoderm and in vivo inhibition of Wnt signaling perturbs neural crest formation. Furthermore, Wnts induce neural crest from naïve neural plates in vitro in a defined medium without added factors, whereas BMPs require additives. Our data suggest that Wnt molecules are necessary and sufficient to induce neural crest cells in avian embryos.

Division of Biology 139-74, California Institute of Technology, Wilson and California, Pasadena, CA 91125, USA.
*   To whom correspondence should be addressed. E-mail: mig1000{at}

dagger    Present address: Developmental Biology Institute, LGPD. Campus de Luminy, case 907 University of Aix-Marseille II, 13288 Marseille Cedex 09, France.

Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos.
C. Milet, F. Maczkowiak, D. D. Roche, and A. H. Monsoro-Burq (2013)
PNAS 110, 5528-5533
   Abstract »    Full Text »    PDF »
BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border.
A. T. Garnett, T. A. Square, and D. M. Medeiros (2012)
Development 139, 4220-4231
   Abstract »    Full Text »    PDF »
Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-{beta} signaling.
C. S. Jayasena and M. E. Bronner (2012)
J. Cell Biol. 199, 453-466
   Abstract »    Full Text »    PDF »
Temporal control of neural crest lineage generation by Wnt/{beta}-catenin signaling.
L. Hari, I. Miescher, O. Shakhova, U. Suter, L. Chin, M. Taketo, W. D. Richardson, N. Kessaris, and L. Sommer (2012)
Development 139, 2107-2117
   Abstract »    Full Text »    PDF »
FGF/MAPK signaling is required in the gastrula epiblast for avian neural crest induction.
T. J. Stuhlmiller and M. I. Garcia-Castro (2012)
Development 139, 289-300
   Abstract »    Full Text »    PDF »
Neural crest specification by noncanonical Wnt signaling and PAR-1.
O. Ossipova and S. Y. Sokol (2011)
Development 138, 5441-5450
   Abstract »    Full Text »    PDF »
Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cells.
L. Menendez, T. A. Yatskievych, P. B. Antin, and S. Dalton (2011)
PNAS 108, 19240-19245
   Abstract »    Full Text »    PDF »
FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk.
P. L. Martinez-Morales, R. Diez del Corral, I. Olivera-Martinez, A. C. Quiroga, R. M. Das, J. A. Barbas, K. G. Storey, and A. V. Morales (2011)
J. Cell Biol. 194, 489-503
   Abstract »    Full Text »    PDF »
Kctd15 inhibits neural crest formation by attenuating Wnt/{beta}-catenin signaling output.
S. Dutta and I. B. Dawid (2010)
Development 137, 3013-3018
   Abstract »    Full Text »    PDF »
Isolation and propagation of enteric neural crest progenitor cells from mouse embryonic stem cells and embryos.
J. Kawaguchi, J. Nichols, M. S. Gierl, T. Faial, and A. Smith (2010)
Development 137, 693-704
   Abstract »    Full Text »    PDF »
The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction.
B. Li, S. Kuriyama, M. Moreno, and R. Mayor (2009)
Development 136, 3267-3278
   Abstract »    Full Text »    PDF »
Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion.
L. Song, Y. Li, K. Wang, Y.-Z. Wang, A. Molotkov, L. Gao, T. Zhao, T. Yamagami, Y. Wang, Q. Gan, et al. (2009)
Development 136, 3161-3171
   Abstract »    Full Text »    PDF »
Folate rescues lithium-, homocysteine- and Wnt3A-induced vertebrate cardiac anomalies.
M. Han, M. C. Serrano, R. Lastra-Vicente, P. Brinez, G. Acharya, J. C. Huhta, R. Chen, and K. K. Linask (2009)
Dis. Model. Mech. 2, 467-478
   Abstract »    Full Text »    PDF »
Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction.
B. Steventon, C. Araya, C. Linker, S. Kuriyama, and R. Mayor (2009)
Development 136, 771-779
   Abstract »    Full Text »    PDF »
Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm.
C.-S. Hong, B.-Y. Park, and J.-P. Saint-Jeannet (2008)
Development 135, 3903-3910
   Abstract »    Full Text »    PDF »
Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of {beta}-catenin in mice.
T. Grigoryan, P. Wend, A. Klaus, and W. Birchmeier (2008)
Genes & Dev. 22, 2308-2341
   Abstract »    Full Text »    PDF »
Insights From a Sea Lamprey Into the Evolution of Neural Crest Gene Regulatory Network.
T. Sauka-Spengler and M. Bronner-Fraser (2008)
Biol. Bull. 214, 303-314
   Abstract »    Full Text »    PDF »
Wnt3a Regulates the Development of Cardiac Neural Crest Cells by Modulating Expression of Cysteine-Rich Intestinal Protein 2 in Rhombomere 6.
X. Sun, R. Zhang, X. Lin, and X. Xu (2008)
Circ. Res. 102, 831-839
   Abstract »    Full Text »    PDF »
Lrig3 regulates neural crest formation in Xenopus by modulating Fgf and Wnt signaling pathways.
H. Zhao, K. Tanegashima, H. Ro, and I. B. Dawid (2008)
Development 135, 1283-1293
   Abstract »    Full Text »    PDF »
Kremen is required for neural crest induction in Xenopus and promotes LRP6-mediated Wnt signaling.
C. Hassler, C.-M. Cruciat, Y.-L. Huang, S. Kuriyama, R. Mayor, and C. Niehrs (2007)
Development 134, 4255-4263
   Abstract »    Full Text »    PDF »
Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain.
C. L. Andoniadou, M. Signore, E. Sajedi, C. Gaston-Massuet, D. Kelberman, A. J. Burns, N. Itasaki, M. Dattani, and J. P. Martinez-Barbera (2007)
Development 134, 1499-1508
   Abstract »    Full Text »    PDF »
Effective Treatment of Tumors with Strong {beta}-Catenin/T-Cell Factor Activity by Transcriptionally Targeted Oncolytic Herpes Simplex Virus Vector..
T. Kuroda, S. D. Rabkin, and R. L. Martuza (2006)
Cancer Res. 66, 10127-10135
   Abstract »    Full Text »    PDF »
Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development.
D. Sakai, T. Suzuki, N. Osumi, and Y. Wakamatsu (2006)
Development 133, 1323-1333
   Abstract »    Full Text »    PDF »
BMP2 and FGF2 cooperate to induce neural-crest-like fates from fetal and adult CNS stem cells.
M. H. M. Sailer, T. G. Hazel, D. M. Panchision, D. J. Hoeppner, M. E. Schwab, and R. D. G. McKay (2005)
J. Cell Sci. 118, 5849-5860
   Abstract »    Full Text »    PDF »
Dynamic Alterations in Gene Expression after Wnt-mediated Induction of Avian Neural Crest.
L. A. Taneyhill and M. Bronner-Fraser (2005)
Mol. Biol. Cell 16, 5283-5293
   Abstract »    Full Text »    PDF »
A balance of FGF, BMP and WNT signalling positions the future placode territory in the head.
A. Litsiou, S. Hanson, and A. Streit (2005)
Development 132, 4051-4062
   Abstract »    Full Text »    PDF »
EWS-FLI1 Fusion Protein Up-regulates Critical Genes in Neural Crest Development and Is Responsible for the Observed Phenotype of Ewing's Family of Tumors.
S. Hu-Lieskovan, J. Zhang, L. Wu, H. Shimada, D. E. Schofield, and T. J. Triche (2005)
Cancer Res. 65, 4633-4644
   Abstract »    Full Text »    PDF »
Essential role of non-canonical Wnt signalling in neural crest migration.
J. De Calisto, C. Araya, L. Marchant, C. F. Riaz, and R. Mayor (2005)
Development 132, 2587-2597
   Abstract »    Full Text »    PDF »
Late-emigrating neural crest cells in the roof plate are restricted to a sensory fate by GDF7.
L. Lo, E. L. Dormand, and D. J. Anderson (2005)
PNAS 102, 7192-7197
   Abstract »    Full Text »    PDF »
Neural crest determination by co-activation of Pax3 and Zic1 genes in Xenopus ectoderm.
T. Sato, N. Sasai, and Y. Sasai (2005)
Development 132, 2355-2363
   Abstract »    Full Text »    PDF »
Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling.
M. Kleber, H.-Y. Lee, H. Wurdak, J. Buchstaller, M. M. Riccomagno, L. M. Ittner, U. Suter, D. J. Epstein, and L. Sommer (2005)
J. Cell Biol. 169, 309-320
   Abstract »    Full Text »    PDF »
Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal.
E. Martinez-Ceballos, P. Chambon, and L. J. Gudas (2005)
J. Biol. Chem. 280, 16484-16498
   Abstract »    Full Text »    PDF »
Wnt-dependent Regulation of the E-cadherin Repressor Snail.
J. I. Yook, X.-Y. Li, I. Ota, E. R. Fearon, and S. J. Weiss (2005)
J. Biol. Chem. 280, 11740-11748
   Abstract »    Full Text »    PDF »
Canonical Wnt activity regulates trunk neural crest delamination linking BMP/noggin signaling with G1/S transition.
T. Burstyn-Cohen, J. Stanleigh, D. Sela-Donenfeld, and C. Kalcheim (2004)
Development 131, 5327-5339
   Abstract »    Full Text »    PDF »
Mesenchymal Stem Cells and the Artery Wall.
M. Abedin, Y. Tintut, and L. L. Demer (2004)
Circ. Res. 95, 671-676
   Abstract »    Full Text »    PDF »
LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest.
S. Perez-Alcala, M. A. Nieto, and J. A. Barbas (2004)
Development 131, 4455-4465
   Abstract »    Full Text »    PDF »
Control of Roof Plate Development and Signaling by Lmx1b in the Caudal Vertebrate CNS.
V. V. Chizhikov and K. J. Millen (2004)
J. Neurosci. 24, 5694-5703
   Abstract »    Full Text »    PDF »
Control of roof plate formation by Lmx1a in the developing spinal cord.
V. V. Chizhikov and K. J. Millen (2004)
Development 131, 2693-2705
   Abstract »    Full Text »    PDF »
Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex.
S. Mercurio, B. Latinkic, N. Itasaki, R. Krumlauf, and J. C. Smith (2004)
Development 131, 2137-2147
   Abstract »    Full Text »    PDF »
Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation.
Y. Yamaguchi, S. Itami, H. Watabe, K.-i. Yasumoto, Z. A. Abdel-Malek, T. Kubo, F. Rouzaud, A. Tanemura, K. Yoshikawa, and V. J. Hearing (2004)
J. Cell Biol. 165, 275-285
   Abstract »    Full Text »    PDF »
Reiterated Wnt signaling during zebrafish neural crest development.
J. L. Lewis, J. Bonner, M. Modrell, J. W. Ragland, R. T. Moon, R. I. Dorsky, and D. W. Raible (2004)
Development 131, 1299-1308
   Abstract »    Full Text »    PDF »
Distinct activities of Msx1 and Msx3 in dorsal neural tube development.
Y. Liu, A. W. Helms, and J. E. Johnson (2004)
Development 131, 1017-1028
   Abstract »    Full Text »    PDF »
DEVELOPMENT: Making Sense of the Sensory Lineage.
M. Bronner-Fraser (2004)
Science 303, 966-968
   Abstract »    Full Text »    PDF »
Instructive Role of Wnt/{beta}-Catenin in Sensory Fate Specification in Neural Crest Stem Cells.
H.-Y. Lee, M. Kleber, L. Hari, V. Brault, U. Suter, M. M. Taketo, R. Kemler, and L. Sommer (2004)
Science 303, 1020-1023
   Abstract »    Full Text »    PDF »
Interplay between Notch signaling and the homeoprotein Xiro1 is required for neural crest induction in Xenopus embryos.
A. Glavic, F. Silva, M. J. Aybar, F. Bastidas, and R. Mayor (2004)
Development 131, 347-359
   Abstract »    Full Text »    PDF »
Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.
C. Tribulo, M. J. Aybar, V. H. Nguyen, M. C. Mullins, and R. Mayor (2003)
Development 130, 6441-6452
   Abstract »    Full Text »    PDF »
Smad4 and {beta}-Catenin Co-activators Functionally Interact with Lymphoid-enhancing Factor to Regulate Graded Expression of Msx2.
S. M. Hussein, E. K. Duff, and C. Sirard (2003)
J. Biol. Chem. 278, 48805-48814
   Abstract »    Full Text »    PDF »
Neural crest development is regulated by the transcription factor Sox9.
M. Cheung and J. Briscoe (2003)
Development 130, 5681-5693
   Abstract »    Full Text »    PDF »
lockjaw encodes a zebrafish tfap2a required for early neural crest development.
R. D. Knight, S. Nair, S. S. Nelson, A. Afshar, Y. Javidan, R. Geisler, G.-J. Rauch, and T. F. Schilling (2003)
Development 130, 5755-5768
   Abstract »    Full Text »    PDF »
Early Vertebrate Evolution of the TATA-Binding Protein, TBP.
A. A. Bondareva and E. E. Schmidt (2003)
Mol. Biol. Evol. 20, 1932-1939
   Abstract »    Full Text »    PDF »
Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a.
G. Castelo-Branco, J. Wagner, F. J. Rodriguez, J. Kele, K. Sousa, N. Rawal, H. A. Pasolli, E. Fuchs, J. Kitajewski, and E. Arenas (2003)
PNAS 100, 12747-12752
   Abstract »    Full Text »    PDF »
Intrinsic signals regulate the initial steps of myogenesis in vertebrates.
C. Linker, C. Lesbros, M. R. Stark, and C. Marcelle (2003)
Development 130, 4797-4807
   Abstract »    Full Text »    PDF »
Wise, a context-dependent activator and inhibitor of Wnt signalling.
N. Itasaki, C. M. Jones, S. Mercurio, A. Rowe, P. M. Domingos, J. C. Smith, and R. Krumlauf (2003)
Development 130, 4295-4305
   Abstract »    Full Text »    PDF »
Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals.
A.-H. Monsoro-Burq, R. B. Fletcher, and R. M. Harland (2003)
Development 130, 3111-3124
   Abstract »    Full Text »    PDF »
Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells.
K. Mizuseki, T. Sakamoto, K. Watanabe, K. Muguruma, M. Ikeya, A. Nishiyama, A. Arakawa, H. Suemori, N. Nakatsuji, H. Kawasaki, et al. (2003)
PNAS 100, 5828-5833
   Abstract »    Full Text »    PDF »
Genomic analysis of neural crest induction.
L. S. Gammill and M. Bronner-Fraser (2003)
Development 129, 5731-5741
   Abstract »    Full Text »    PDF »
Snail precedes Slug in the genetic cascade required for the specification and migration of the Xenopus neural crest.
M. J. Aybar, M. A. Nieto, and R. Mayor (2003)
Development 130, 483-494
   Abstract »    Full Text »    PDF »
Induction of neural crest in Xenopus by transcription factor AP2{alpha}.
T. Luo, Y.-H. Lee, J.-P. Saint-Jeannet, and T. D. Sargent (2003)
PNAS 100, 532-537
   Abstract »    Full Text »    PDF »
DEVELOPMENT: Riding the Crest of the Wnt Signaling Wave.
P. Trainor and R. Krumlauf (2002)
Science 297, 781-783
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882