Fam46a regulates BMP-dependent pre-placodal ectoderm differentiation in Xenopus

The pre-placodal ectoderm (PPE) is a specialized ectodermal region which gives rise to the sensory organs and other systems. The PPE is induced from the neural plate border (NPB) during neurulation, but the molecular mechanism of PPE formation is not fully understood. In this study, we examined the role of a newly identified PPE gene, Fam46a, during embryogenesis. Fam46a contains a nucleoside triphosphate (NTP) transferase domain, but its function in early development was previously unclear. We showed that Fam46a is expressed in the PPE in Xenopus embryos, and Fam46a knockdown induces the abnormalities in the eye formation and the body color. At the neurula stage, Fam46a upregulates the expression of PPE genes and inhibits neural crest (NC) formation. We also showed that Fam46a physically interacts with Smad1/Smad4 and positively regulates BMP signaling. From these results, we concluded that Fam46a is required for PPE formation via the positive regulation of BMP signaling. Our study provides a new mechanism of ectodermal patterning via cell-autonomous regulation of BMP signaling in the PPE.