Tbx3 represses bmp4 expression and, with Pax6, is required and sufficient for retina formation

Vertebrate eye formation begins in the anterior neural plate in the eye field. Seven eye field transcription factors (EFTFs) are expressed in eye field cells and when expressed together are sufficient to generate retina from pluripotent cells. The EFTF Tbx3 can regulate the expression of some EFTFs; however, its role in retina formation is unknown. Here, we show that Tbx3 represses bmp4 transcription and is required in the eye field for both neural induction and normal eye formation in Xenopus laevis. Although sufficient for neural induction, Tbx3-expressing pluripotent cells only form retina in the context of the eye field. Unlike Tbx3, the neural inducer Noggin can generate retina both within and outside the eye field. We found that the neural and retina-inducing activity of Noggin requires Tbx3. Noggin, but not Tbx3, induces Pax6 and coexpression of Tbx3 and Pax6 is sufficient to determine pluripotent cells to a retinal lineage. Our results suggest that Tbx3 represses bmp4 expression and maintains eye field neural progenitors in a multipotent state; then, in combination with Pax6, Tbx3 causes eye field cells to form retina.