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XB-ART-39705
Development March 1, 2009; 136 (5): 771-9.

Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction.

Steventon B , Araya C , Linker C , Kuriyama S , Mayor R .


Abstract
The neural crest is induced by a combination of secreted signals. Although previous models of neural crest induction have proposed a step-wise activation of these signals, the actual spatial and temporal requirement has not been analysed. Through analysing the role of the mesoderm we show for the first time that specification of neural crest requires two temporally and chemically different steps: first, an induction at the gastrula stage dependent on signals arising from the dorsolateral mesoderm; and second, a maintenance step at the neurula stage dependent on signals from tissues adjacent to the neural crest. By performing tissue recombination experiments and using specific inhibitors of different inductive signals, we show that the first inductive step requires Wnt activation and BMP inhibition, whereas the later maintenance step requires activation of both pathways. This change in BMP necessity from BMP inhibition at gastrula to BMP activation at neurula stages is further supported by the dynamic expression of BMP4 and its antagonists, and is confirmed by direct measurements of BMP activity in the neural crest cells. The differential requirements of BMP activity allow us to propose an explanation for apparently discrepant results between chick and frog experiments. The demonstration that Wnt signals are required for neural crest induction by mesoderm solves an additional long-standing controversy. Finally, our results emphasise the importance of considering the order of exposure to signals during an inductive event.

PubMed ID: 19176585
PMC ID: PMC2685944
Article link: Development
Grant support: [+]
Genes referenced: akr1c2 bmp4 chrd.1 dkk1 gsk3b nog snai2 sox2 wnt8a
Morpholinos: chrd MO1


Article Images: [+] show captions
References [+] :
Aybar, Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. 2002, Pubmed, Xenbase


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