A Caenorhabditis elegans model for epithelial–neuronal transdifferentiation

doi:10.1073/pnas.0712159105

A Caenorhabditis elegans model for epithelial–neuronal transdifferentiation

*Department of Cell and Developmental Biology and
^§Electron Microscopy Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U596, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7104, F-67404 Illkirch, France;
^†Université Louis Pasteur, F-67000 Strasbourg, France; and
^¶Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032

Contributed by Iva Greenwald, December 22, 2007 (received for review December 12, 2007)

Abstract

Understanding transdifferentiation—the conversion of one differentiated cell type into another—is important from both basic science and clinical perspectives. In Caenorhabditis elegans, an epithelial cell named Y is initially part of the rectum but later appears to withdraw, migrate, and then become a motor neuron named PDA. Here, we show that this represents a bona fide transdifferentiation event: Y has epithelial hallmarks without detectable neural characteristics, and PDA has no residual epithelial characteristics. Using available mutants and laser microsurgery, we found that transdifferentiation does not depend on fusion with a neighboring cell or require migration of Y away from the rectum, that other rectal epithelial cells are not competent to transdifferentiate, and that transdifferentiation requires the EGL-5 and SEM-4 transcription factors and LIN-12/Notch signaling. Our results establish Y-to-PDA transdifferentiation as a genetically tractable model for deciphering the mechanisms underlying cellular plasticity in vivo.

Footnotes

^‡To whom correspondence may be addressed at:
Department of Cell and Developmental Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, BP 10142, Illkirch Cedex 67404, France.
E-mail: sophie{at}igbmc.u-strasbg.fr
^‖To whom correspondence may be addressed. E-mail: greenwald{at}cancercenter.columbia.edu
Author contributions: S.J. designed research; S.J. and Y.S. performed research; S.J. contributed new reagents/analytic tools; S.J. and I.G. analyzed data; and S.J. and I.G. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0712159105/DC1.