Regenerating the Flatworm....it's (perpetually) alive!

"Modeling Planarian Regeneration: A Primer for Reverse-Engineering the Worm" is a recently-published paper (in the "Perspectives" category) in PLoS Computational Biology [1]. It is a really interesting take on regenerative biology from Michael Levin's group at Tufts University. I recently gave a talk to Levin's group [2], and highly recommend his work.

Figure 1. Morphology of the Flatworm (Planarian) -- a popular model organism for regenerative medicine. COURTESY: Figure 1 in [1].

Work done in the Levin group is a mix of electrophysiology, developmental biology, and computational modeling. One example of this is a perceptron-like algebraic expression [3] Levin has derived for understanding the sources of variation that go into regeneration. For example, regeneration (viewed as an output) is a function of several inputs.

Figure 2. Michael Levin's "formula" for regeneration. COURTESY: Figure 1, [3], also [4].

The best part of this paper is a systematic review of what different types of perturbations can do to a planarian's body. For example, what is the effect of amputation? Or dietary restriction? Or gap junction blockage? Figure 3 shows the consequences of seven different types of perturbation (injury and/or environmental effects). You should also be aware that Planaria are somewhat unique in their ability to regenerate in a totipotent fashion (their neoblasts have the potential to generate an entirely new organism) [see 5]. In fact, some rather incredible work has been done in the world of regenerative biology using Planarians as a model [6].

Figure 3. Different perturbation applied to the flatworm morphopology and the organism's ability to regenerate. COURTESY: Figure 2, [1].

Again, not all regenerative systems are dependent on totipotency. For example, regeneration in amphibians and fishes occurs in entire limbs based on the coordinated activity of existing tissues and pluripotent cell types [7, 8]. But Levin does incorporate his own group's work here -- which is driving forward our understanding of the connection between regeneration and electrophysiology (e.g. disturbing membrane voltages and applied electrical fields). I have also referenced an instructional review I did a few months back highlighting several of Levin's papers, in which I highlighted the connections between electrophysiology, regeneration, and developmental plasticity to a general scientific audience [4]. 

References:

[1] Lobo, D., Beane, W.S., and Levin, M. (2012). Modeling Planarian Regeneration: A Primer for Reverse-Engineering the Worm. PLoS Computational Biology, 8(4), e1002481.

[2] "Advancing Dynamic Models of Cellular Processes (and new ways to fund them)". Figshare, doi:10.6084/m9.figshare.701464 (2012).

[3] Levin, M. (2009). Bioelectric mechanisms in regeneration: unique aspects and future perspectives. Seminars in Cell and Developmental Biology, 20, 543-556.

[4] Alicea, B. (2012). Bioelectric Processes of Cellular Plasticity and Regeneration. Stem Cell and Regenerative Medicine Journal Club, Cellular Reprogramming Laboratory.

Lecture: http://www.msu.edu/~aliceabr/bioe-cellular-plasticity.pdf

[5] Baguna, J, Salo, E., and Auladell, C. (1989). Regeneration and pattern formation in planarians. III. Development, 107, 77-86.

[6] Wagner, D.E. et.al (2011). Clonogenic Neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science, 332, 811.

[7] Brockes, J.P. and Kumar, A. (2002). Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nature Reviews Molecular Cell Biology 3, 566-574.

[8] King, R.S. and Newmark, P.K. (2012). The cell biology of regeneraion. Journal of Cell Biology, 196(5), 553-562.