Coordinated genomic control of ciliogenesis and cell movement by RFX2

Elife. 2014;3:e01439. doi: 10.7554/eLife.01439. Epub 2014 Jan 14.

Abstract

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. DOI: http://dx.doi.org/10.7554/eLife.01439.001.

Keywords: Rfx2; cilia; cilia beating; genomics; mucociliary epithelium; multiciliated cells; nme5; protofilament ribbon; ribc2; ttc29.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Cell Movement / genetics*
  • Cilia / metabolism
  • Computational Biology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Databases, Genetic
  • Embryo, Nonmammalian / metabolism
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Humans
  • Morphogenesis
  • Regulatory Factor X Transcription Factors
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Xenopus Proteins / genetics*
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology

Substances

  • DNA-Binding Proteins
  • RFX2 protein, Xenopus
  • RFX2 protein, human
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • Xenopus Proteins