A Caenorhabditis elegans model for epithelial-neuronal transdifferentiation

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.

Fig. 1.

The Y-to-PDA transition in wild type and mutants. (A) Y is part of the rectum in the L1 stage. The rectum is composed of three rings of two cells each. In the L1 stage, the most anterodorsal ring is made of the cells K and K′, the middle ring is made of U and F, and the posteroventral-most ring is made of Y and B. (B) Stages and timing of Y-to-PDA transdifferentiation relative to somatic gonad development. The somatic precursors, Z1 and Z4, undergo three rounds of divisions, and the differentiated anchor cell is evident when the primordium forms (41). We correlated milestones in Y-to-PDA transdifferentiation with somatic gonadal development. Depicted is Y's nucleus migration and morphology change during the process. The position of the nuclei (and nucleoli) of the rectal cells, PDA, and P11.p, the other epithelial cell found near the anterior rectum, as seen by Nomarski optics, are represented as well as the PDA axon (blue dotted line). In this figure and all others, anterior is to the left, and ventral is to the bottom.

Fig. 2.

Ultrastructural characteristics of Y. (A) Electron micrograph of the rectal area of a newly hatched L1 hermaphrodite showing the B and the Y cells (outlined in black and red, respectively) wrapped around the rectum, both displaying a train-rail-like shape. (Inset) The section of the whole worm from which the rectal area is magnified in A. (B) Blow-up of the boxed area in A, illustrating a C. elegans junction (arrowhead) between the apical membranes of Y and B. (C) Another section of the same L1 animal illustrating a junction between the apical side of the Y cell, or the B cell, and the cuticle of the rectum (arrows). This structure is called a fibrous organelle in C. elegans. An asterisk indicates the rectal slit.