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XB-ART-40487
Development October 1, 2009; 136 (19): 3267-78.

The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction.

Li B , Kuriyama S , Moreno M , Mayor R .


Abstract
Wnt signalling is required for neural crest (NC) induction; however, the direct targets of the Wnt pathway during NC induction remain unknown. We show here that the homeobox gene Gbx2 is essential in this process and is directly activated by Wnt/beta-catenin signalling. By ChIP and transgenesis analysis we show that the Gbx2 regulatory elements that drive expression in the NC respond directly to Wnt/beta-catenin signalling. Gbx2 has previously been implicated in posteriorization of the neural plate. Here we unveil a new role for this gene in neural fold patterning. Loss-of-function experiments using antisense morpholinos against Gbx2 inhibit NC and expand the preplacodal domain, whereas Gbx2 overexpression leads to transformation of the preplacodal domain into NC cells. We show that the NC specifier activity of Gbx2 is dependent on the interaction with Zic1 and the inhibition of preplacodal genes such as Six1. In addition, we demonstrate that Gbx2 is upstream of the neural fold specifiers Pax3 and Msx1. Our results place Gbx2 as the earliest factor in the NC genetic cascade being directly regulated by the inductive molecules, and support the notion that posteriorization of the neural folds is an essential step in NC specification. We propose a new genetic cascade that operates in the distinction between anterior placodal and NC territories.

PubMed ID: 19736322
PMC ID: PMC2808295
Article link: Development
Grant support: [+]
Genes referenced: akr1c1 bmp4 dvl1 dvl2 en2 foxd3 gbx2.1 gbx2.2 krt12.4 msx1 odc1 otx2 pax3 ptgds six1 snai2 sox2 sox9 zic1
Morpholinos: gbx2.1 MO1 gbx2.2 MO1


Article Images: [+] show captions
References:
Ahrens, 2005, Pubmed, Xenbase [+]


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