Li, B; (2015) Posteriorizing factor Gbx2 is a direct target of Wnt signalling during neural crest induction. Doctoral thesis , UCL (University College London).

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Abstract

Wnt signalling is required for neural crest induction; however the direct targets of the Wnt pathway during neural crest induction remain unknown. I show here that the homeobox gene Gbx2 is essential in this process and is directly activated by Wnt/β-catenin signalling. Gbx2 has previously been implicated in posteriorization of the neural plate. Here I unveil a new role for this gene in neural fold patterning. Loss of function experiments using antisense morpholinos against Gbx2 inhibit neural crest and expand the preplacodal domain, while Gbx2 over expression leads to transformation of the preplacodal domain into neural crest cells. I show that the neural crest specifier activity of Gbx2 is dependent on the interaction with Zic1 and the inhibition of preplacodal genes such as Six1. In addition, I demonstrate that Gbx2 is upstream of the neural fold specifiers Pax3 and Msx1. My results place Gbx2 upstream of the neural crest genetic cascade being directly regulated by the inductive molecules, and support the notion that posteriorization of the neural folds is an essential step in neural crest specification. I propose a new genetic cascade that operates in the distinction between preplacodal and neural crest territories.

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