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Noelins modulate the timing of neuronal differentiation during development

Moreno, Tanya A. and Bronner-Fraser, Marianne (2005) Noelins modulate the timing of neuronal differentiation during development. Developmental Biology, 288 (2). pp. 434-447. ISSN 0012-1606. doi:10.1016/j.ydbio.2005.09.050.

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Noelins comprise a family of extracellular proteins with proposed roles in neural and neural crest development. Here, we show that a previously uncharacterized family member, Noelin-4, functions to maintain neural precursors in an undifferentiated state and biases ectoderm toward a neural fate. We show that Noelin-4 is induced by the neurogenic genes X-ngnr-1 and XNeuroD. Over-expression of Noelin-4 causes expansion of the neural plate at the expense of neural crest and epidermis. Although there is an apparent increase in the neural precursor pool, no increase was noted in differentiated neurons. Later, derivatives such as the neural tube and retina appear enlarged. We show biochemically that Noelin-4 protein is glycosylated and secreted and that it interacts with Noelin-1, an isoform previously found to promote differentiation in neuralized animal caps. Accordingly, the neural precursor expansion activity of Noelin-4 is reversed by co-expression of Noelin-1. Our finding that Noelin isoforms can bind to and antagonize one another suggests that interacting Noelin isoforms may play a role in regulating timing of differentiation.

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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 2005 Elsevier Inc. Received for publication 3 August 2005, revised 9 September 2005, accepted 21 September 2005. Available online 14 November 2005. We are grateful to Drs. Clare Baker, Laura Gammill, Anne Knecht and Carole LaBonne for critical reading of the manuscript and helpful discussions during the course of this work. We thank Johanna Tan who provided excellent technical assistance. cDNA libraries and constructs used were kind gifts of R. Harland, M. King, and Y. Sasai. T.A.M. was a fellow of the ARCS foundation. This work was supported by NIH grant NS42287 to M.B.-F.
Funding AgencyGrant Number
Subject Keywords:Noelin-4; Noelin-1; Neurogenesis; Xenopus; Neural competence; Neural differentiation
Issue or Number:2
Record Number:CaltechAUTHORS:20160121-103519913
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Official Citation:Tanya A. Moreno, Marianne Bronner-Fraser, Noelins modulate the timing of neuronal differentiation during development, Developmental Biology, Volume 288, Issue 2, 15 December 2005, Pages 434-447, ISSN 0012-1606, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63837
Deposited By: Ruth Sustaita
Deposited On:21 Jan 2016 19:21
Last Modified:10 Nov 2021 23:22

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