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The Secreted Glycoprotein Noelin-1 Promotes Neurogenesis in Xenopus

Moreno, Tanya A. and Bronner-Fraser, Marianne (2001) The Secreted Glycoprotein Noelin-1 Promotes Neurogenesis in Xenopus. Developmental Biology, 240 (2). pp. 340-360. ISSN 0012-1606. doi:10.1006/dbio.2001.0472.

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Neurogenesis in Xenopus neural ectoderm involves multiple gene families, including basic helix-loop-helix transcription factors, which initiate and control primary neurogenesis. Equally important, though less well understood, are the downstream effectors of the activity of these transcription factors. We have investigated the role of a candidate downstream effector, Noelin-1, during Xenopus development. Noelin-1 is a secreted glycoprotein that likely forms large multiunit complexes. In avians, overexpression of Noelin-1 causes prolonged and excessive neural crest migration. Our studies in Xenopus reveal that this gene, while highly conserved in sequence, has a divergent function in primary neurogenesis. XenopusNoelin-1 is expressed mainly by postmitotic neurogenic tissues in the developing central and peripheral nervous systems, first appearing after neural tube closure. Its expression is upregulated in ectopic locations upon overexpression of the neurogenic genes X-ngnr-1 and XNeuroD. Noelin-1 expression in animal caps induces expression of neural markers XBrn-3d and XNeuroD, and co-expression of secreted Noelin-1 with noggin amplifies noggin-induced expression of XBrn-3d and XNeuroD. Furthermore, in animal caps neuralized by expression of noggin, co-expression of Noelin-1 causes expression of neuronal differentiation markers several stages before neurogenesis normally occurs in this tissue. Finally, only secreted forms of the protein can activate sensory marker expression, while all forms of the protein can induce early neurogenesis. This suggests that the cellular localization of Noelin-1 may be important to its function. Thus, Noelin-1 represents a novel secreted factor involved in neurogenesis.

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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 2001 Elsevier Science. Received for publication June 20, 2001. Revised September 6, 2001. Accepted September 10, 2001. Published online November 14, 2001. The authors gratefully acknowledge Drs. A. Knecht, L. Gammill and C. Baker for critically reading the manuscript; C. Baker, L. Gammill, A. Knecht, members of the laboratory and especially C. LaBonne for support, valuable insights and discussion. C. LaBonne kindly assisted with oocyte labeling experiments. The authors thank the following for their kind gifts of reagents: Drs. R Harland for the Xenopus cDNA library; D. Anderson, X-ngnr-1; A. Brändli, Pax-2; K. Cho, 6-myc-Noggin; C. Kintner, N-tubulin; J. Lee, XNeuroD; R. Mayor, Xslug. The authors also thank the anonymous reviewers for helpful comments. T.A.M. is a Fellow of the ARCS Foundation. This work was supported by USPHS grants NS36585 and NS41070.
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Subject Keywords:Noelin-1; Xenopus laevis; Noggin; primary neurogenesis; cranial ganglia; XBrn-3d; NeuroD; N-tubulin; neural crest; placodes
Issue or Number:2
Record Number:CaltechAUTHORS:20160114-101925673
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Official Citation:Tanya A. Moreno, Marianne Bronner-Fraser, The Secreted Glycoprotein Noelin-1 Promotes Neurogenesis in Xenopus, Developmental Biology, Volume 240, Issue 2, 15 December 2001, Pages 340-360, ISSN 0012-1606, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63682
Deposited By: Ruth Sustaita
Deposited On:14 Jan 2016 19:24
Last Modified:10 Nov 2021 23:20

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