The activity of Pax3 and Zic1 regulates three distinct cell fates at the neural plate border

In Xenopus, the neural plate border gives rise to at least three cell populations: the neural crest, the preplacodal ectoderm, and the hatching gland. To understand the molecular mechanisms that regulate the formation of these lineages, we have analyzed the role of two transcription factors, Pax3 and Zic1, which are among the earliest genes activated in response to neural plate border-inducing signals. At the end of gastrulation, Pax3 and Zic1 are coexpressed in the neural crest forming region. In addition, Pax3 is expressed in progenitors of the hatching gland, and Zic1 is detected in the preplacodal ectoderm. Using gain of function and knockdown approaches in whole embryos and animal explants, we demonstrate that Pax3 and Zic1 are necessary and sufficient to promote hatching gland and preplacodal fates, respectively, whereas their combined activity is essential to specify the neural crest. Moreover, we show that by manipulating the levels of Pax3 and Zic1 it is possible to shift fates among these cells. These findings provide novel information on the mechanisms regulating cell fate decisions at the neural plate border.