Coordinated genomic control of ciliogenesis and cell movement by RFX2
Mei-I Chung,
Taejoon Kwon,
Fan Tu,
Eric R Brooks,
Rakhi Gupta,
Matthew Meyer,
Julie C Baker,
Edward M Marcotte,
John B Wallingford
Affiliations
Mei-I Chung
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
Taejoon Kwon
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
Fan Tu
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
Eric R Brooks
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
Rakhi Gupta
Department of Genetics, Stanford University, Stanford, United States
Matthew Meyer
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States
Julie C Baker
Department of Genetics, Stanford University, Stanford, United States
Edward M Marcotte
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, United States; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
John B Wallingford
Department of Molecular Biosciences, University of Texas at Austin, Austin, United States; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, United States; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States; Howard Hughes Medical Institute, University of Texas at Austin, Austin, United States
The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood. In this study, we have defined such a program for multi-ciliated epithelial cells (MCCs), a cell type critical for proper development and homeostasis of the airway, brain and reproductive tracts. Starting from genomic analysis of the cilia-associated transcription factor Rfx2, we used bioinformatics and in vivo cell biological approaches to gain insights into the molecular basis of cilia assembly and function. Moreover, we discovered a previously un-recognized role for an Rfx factor in cell movement, finding that Rfx2 cell-autonomously controls apical surface expansion in nascent MCCs. Thus, Rfx2 coordinates multiple, distinct gene expression programs in MCCs, regulating genes that control cell movement, ciliogenesis, and cilia function. As such, the work serves as a paradigm for understanding genomic control of cell biological processes that span from early cell morphogenetic events to terminally differentiated cellular functions.
