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Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer

Pinho, S; Simonsson, PR; Trevers, KE; Stower, MJ; Sherlock, WT; Khan, M; Streit, A; ... Stern, CD; + view all (2011) Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer. PLOS ONE , 6 (4) , Article e19157. 10.1371/journal.pone.0019157. Green open access

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Abstract

The amniote organizer (Hensen's node) can induce a complete nervous system when grafted into a peripheral region of a host embryo. Although BMP inhibition has been implicated in neural induction, non-neural cells cannot respond to BMP antagonists unless previously exposed to a node graft for at least 5 hours before BMP inhibitors. To define signals and responses during the first 5 hours of node signals, a differential screen was conducted. Here we describe three early response genes: two of them, Asterix and Obelix, encode previously undescribed proteins of unknown function but Obelix appears to be a nuclear RNA-binding protein. The third is TrkC, a neurotrophin receptor. All three genes are induced by a node graft within 4-5 hours but they differ in the extent to which they are inducible by FGF: FGF is both necessary and sufficient to induce Asterix, sufficient but not necessary to induce Obelix and neither sufficient nor necessary for induction of TrkC. These genes are also not induced by retinoic acid, Noggin, Chordin, Dkk1, Cerberus, HGF/SF, Somatostatin or ionomycin-mediated Calcium entry. Comparison of the expression and regulation of these genes with other early neural markers reveals three distinct "epochs'', or temporal waves, of gene expression accompanying neural induction by a grafted organizer, which are mirrored by specific stages of normal neural plate development. The results are consistent with neural induction being a cascade of responses elicited by different signals, culminating in the formation of a patterned nervous system.

Type: Article
Title: Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0019157
Publisher version: http://dx.doi.org/10.1371/journal.pone.0019157
Language: English
Additional information: © 2011 Pinho et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was funded by grants from the Medical Research Council and the National Institutes of Health (USA) (R01MH60156). SP was part of the GABBA Programme, University of Porto and was supported by the Portuguese Foundation for Science and Technology (FCT). PRS was supported by a BBSRC quota studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: TRANSLATION INITIATION-FACTORS, PRIMITIVE STREAK FORMATION, MESSENGER-RNA EXPRESSION, IN-SITU HYBRIDIZATION, CHICK-EMBRYO, BMP INHIBITION, AVIAN EMBRYOS, XENOPUS-LAEVIS, SPEMANN ORGANIZER, RETINOIC ACID
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1306840
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