mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes

• DOI: 10.1038/ncomms7017
• Publication Date: 2015-01-19T10:12:45Z
• Authors: Chika Takahashi; Morioh Kusakabe; Toshiyasu Suzuki; Koichi Miyatake; Eisuke Nishida
• Keywords: 0301 basic medicine; Embryo, Nonmammalian; Receptors, Notch; Gene Expression Regulation, Developmental; Cell Differentiation; Epithelial Cells; Xenopus Proteins; Cell Line; Mice; Xenopus laevis; 03 medical and health sciences; Epidermal Cells; Animals

Cell fate specifications of multiciliate cells (MCCs) and ionocytes are commonly suppressed by the Notch pathway in developing epithelia, but are governed by different master regulators, suggesting the existence of a common regulator linking the Notch pathway to both MCC and ionocyte specifications. Here we show that a mab21 family gene, mab21-l3, represents the missing link. In Xenopus embryonic epidermis, mab21-l3 expression is specifically found in MCCs and ionocytes and is downregulated by the Notch pathway. Knockdown of mab21-l3 in Xenopus downregulates both MCC-specific and ionocyte-specific master genes, resulting in drastic loss of MCCs and ionocytes. In mouse tracheal epithelial cells, mab21-l3 expression is also downregulated by the Notch pathway and is required for MCC differentiation. Moreover, conditional gain of function of mab21-l3 rescues Notch-induced loss of MCCs and ionocytes in Xenopus. These results indicate that mab21-l3 acts downstream of the Notch pathway in cell fate specifications of MCCs and ionocytes.