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Noelin-1 is a secreted glycoprotein involved in generation of the neural crest

Abstract

The vertebrate neural crest arises at the border of the neural plate during early stages of nervous system development; however, little is known about the molecular mechanisms underlying neural crest formation. Here we identify a secreted protein, Noelin-1, which has the ability to prolong neural crest production. Noelin-1 messenger RNA is expressed in a graded pattern in the closing neural tube. It subsequently becomes restricted to the dorsal neural folds and migrating neural crest. Over expression of Noelin-1 using recombinant retroviruses causes an excess of neural crest emigration and extends the time that the neural tube is competent to generate as well as regenerate neural crest cells. These results support an important role for Noelin-1 in regulating the production of neural crest cells by the neural tube.

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Figure 1: Expression pattern of Noelin-1 in the early chick embryo revealed by in situ hybridization.
Figure 2: Expression pattern of Noelin-1 in stage 1415 embryos.
Figure 3: Molecular characteristics of Noelin.
Figure 4: Effects of Noelin-1 overexpression on generation of neural crest cells.
Figure 5: Overexpression of Noelin-1 increases neural crest production at the level of r3.
Figure 6: Effects of overexpression of Noelin-2 on neural crest production by the neural tube.
Figure 7: Noelin-1 prolongs the ability of the neural tube to regenerate neural crest cells and functions non-cell-autonomously.
Figure 8: Overexpression of Noelin-1 upregulates Slug expression but not other dorsoventral neural tube markers.

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Acknowledgements

We thank C. Baker, S. Fraser, M. Dickinson, B. Murray and M. Selleck for helpful discussions and comments on the manuscript and J. Neri and R. Velasco for help with sectioning. This work was supported by NS 36585 and NS 34671.

Correspondence and requests for materials should be addressed to M.B-F.

Sequences for Noelin-1 and Noelin-2 have been deposited in GenBank (accession nos AF182815 and AF239804, respectively).

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Correspondence to Marianne Bronner-Fraser.

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Barembaum, M., Moreno, T., LaBonne, C. et al. Noelin-1 is a secreted glycoprotein involved in generation of the neural crest. Nat Cell Biol 2, 219–225 (2000). https://doi.org/10.1038/35008643

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