Two different types of neurulation processes take place during early embryogenesis. One is a well known neurulation where a sheet of epithelial cells folds inward to form a tubular structure (primary neurulation). Another one, called secondary neurulation (SN), is seen in a posterior region of the body. SN proceeds by mesenchymal-to-epithelial transition (MET), the process contrasting with that of the primary neurulation. Although the SN was histologically described more than 70 years ago, its molecular- and cellular mechanisms remain unknown. SN precursor cells are generated during gastrulation from ingressing cells (mesenchymal) that also give rise to presomitic mesoderm (PSM). This raises two questions: What discriminates SN from PSM? And how mesenchymal cells undergo epithelialization during the SN? To address these questions, we have focused on two transcriptional factors, Pax2 expressed in SN-region and Tbx6L in PSM, to perform tissue-specific gene manipulation using chicken embryos. We have found that Pax2 and Tbx6L play important roles in the formation of SN and PSM, respectively, by counteracting each other. Remarkably, Pax2, when overexpressed in PSM, causes ectopic formation of SN-like neural tube. Furthermore, Tbx6L impedes SN formation when expressed in a presumptive SN. These findings suggest that during the SN processes, Pax2 represses mesodermal genes (i.e. Tbx6L), and regulates a set of genes important for cell epithelialization and tubular formation. We will also discuss a possible link of SN to Hox gene regulation in the construction of posterior body structures.