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Specification of the neural crest occurs during gastrulation and requires Pax7

Nature volume 441, pages 218–222 (2006)Cite this article

Abstract

The neural crest is a stem population critical for development of the vertebrate craniofacial skeleton and peripheral ganglia. Neural crest cells originate along the border between the neural plate and epidermis1, migrate extensively and generate numerous derivatives, including neurons and glia of the peripheral nervous system, melanocytes, bone and cartilage of the head skeleton2. Impaired neural crest development is associated with human defects, including cleft palate3. Classically, the neural crest has been thought to form by interactions at the border between neural and non-neural ectoderm or mesoderm4,5,6,7, and defined factors such as bone morphogenetic proteins (BMPs) and Wnt proteins have been postulated as neural crest-inducers8,9,10,11,12,13. Although competence to induce crest cells declines after stage 10 (ref. 14), little is known about when neural crest induction begins in vivo. Here we report that neural crest induction is underway during gastrulation and well before proper neural plate appearance. We show that a restricted region of chick epiblast (stage 3–4) is specified to generate neural crest cells when explanted under non-inducing conditions. This region expresses the transcription factor Pax7 by stage 4 + and later contributes to neural folds and migrating neural crest. In chicken embryos, Pax7 is required for neural crest formation in vivo, because blocking its translation inhibits expression of the neural crest markers Slug, Sox9, Sox10 and HNK-1. Our results indicate that neural crest specification initiates earlier than previously assumed, independently of mesodermal and neural tissues, and that Pax7 has a crucial function during neural crest development.

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Figure 1: Early expression of Pax7 in presumptive neural crest from gastrulation to neurulation.
Figure 2: Neural crest stem cells are specified at stage 3, independently of neural and mesodermal tissues.
Figure 3: Pax7 is required for early neural crest formation in vivo.

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Acknowledgements

We thank A. Streit, S. Fraser, A. Groves, L. Gammill, V. Lee, J. Sechrist and T. Moreno for comments and discussions; S. Mackem, D. Wilkinson, E. Matsunaga, A. Kawakami, O. Pourquié and H. Kondoh for gifts of Tbx6l, cMsx1, full-length cPax3, full-length cPax7, BMP4, Sox2, Dlx5 and Gata2 probes and constructs; and D. Arce and Y. Liu for technical assistance. This work was supported by a USPHS grant to M.B.-F.

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  1. Martín L. Basch

    Present address: CMB Department, House Ear Institute, 2100 W 3rd Street, Los Angeles, California, 90029, USA

Authors and Affiliations

  1. Division of Biology 139-74, California Institute of Technology, Pasadena, California, 91125, USA

    Martín L. Basch, Marianne Bronner-Fraser & Martín I. García-Castro

  2. MCDB Yale University, New Haven, PO Box 208103, Connecticut, 06520-8103, USA

    Martín I. García-Castro

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  1. Martín L. Basch
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Correspondence to Martín I. García-Castro.

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This file contains Supplementary Figures 1 and 2 and Supplementary Table 1. (DOC 1844 kb)

Supplementary Methods

This file contains additional details of the methods used in this study. (DOC 23 kb)

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Basch, M., Bronner-Fraser, M. & García-Castro, M. Specification of the neural crest occurs during gastrulation and requires Pax7. Nature 441, 218–222 (2006). https://doi.org/10.1038/nature04684

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