Fam46a is a regulator for gene expression in secretory tissues and plays an important role in development and homeostasis [Fam46a-MO1]

In early embryonic development, the organiser functions in multiple developmental processes, including neural induction, dorsoventral patterning of the mesoderm, and formation of the axial mesoderm. Chordin is a central molecule for the activity of the Spemann’s organiser and abundantly secreted from the Spemann’s organiser in Xenopus laevis. However, so far, a whole picture of the gene expression profile regulated by Chordin has not been examined. Here, we perform microarray analysis of chordin overexpression and identify fam46a as an upregulated gene. We demonstrate that fam46a is essential for Xenopus laevis early embryonic development as well as gene induction during cell differentiation in mammalian cell culture models. fam46a is preferentially expressed in tissues with high secretory ability. In Xenopus laevis, fam46a is required for normal neural tube closure and expression of epidermal markers, neural markers and mesodermal markers. In the human Caco-2 cell model, FAM46A is localised in the nucleus and cytoplasm, and regulates gene induction during cell differentiation. In the mouse intestinal organoid model, Fam46a is required for survival of organoids as well as enterocyte differentiation. These results indicate that fam46a is a regulator for gene expression in secretory cells during cell differentiation in early embryonic development and adult homeostasis. To analyse which genes were affected by fam46a depletion in the Xenopus laevis embryo, we performed microarray analysis on fam46a depleted embryos. CoMO (10 ng/cell), Fam46a-MO1 (10 ng/cell) or Fam46a-MO2 (7 ng/cell) plus Fam46-MO3 (7 ng/cell) was injected into the animal pole of all blastomeres at the four-cell stage.