TY  - JOUR
N1  - © 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.
IS  - 4
Y1  - 2011/04/29/
AV  - public
VL  - 6
TI  - Distinct Steps of Neural Induction Revealed by Asterix, Obelix and TrkC, Genes Induced by Different Signals from the Organizer
KW  - TRANSLATION INITIATION-FACTORS
KW  -  PRIMITIVE STREAK FORMATION
KW  -  MESSENGER-RNA EXPRESSION
KW  -  IN-SITU HYBRIDIZATION
KW  -  CHICK-EMBRYO
KW  -  BMP INHIBITION
KW  -  AVIAN EMBRYOS
KW  -  XENOPUS-LAEVIS
KW  -  SPEMANN ORGANIZER
KW  -  RETINOIC ACID
A1  - Pinho, S
A1  - Simonsson, PR
A1  - Trevers, KE
A1  - Stower, MJ
A1  - Sherlock, WT
A1  - Khan, M
A1  - Streit, A
A1  - Sheng, GJ
A1  - Stern, CD
JF  - PLOS ONE
SN  - 1932-6203
PB  - PUBLIC LIBRARY SCIENCE
UR  - http://dx.doi.org/10.1371/journal.pone.0019157
ID  - discovery1306840
N2  - 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.
ER  -