After injury, an organism must mount a series of responses to minimize and — if possible — repair damage. Some organisms regenerate poorly, while others (including humans) regenerate to differing degrees depending on the tissue that is damaged. Rarely, organisms possess the ability to repair or regenerate any missing tissue. Organisms with remarkable regenerative power include planarians, which are flatworms that can regrow missing tissues after a wide range of amputations or injuries.
In our lab, we use planarians to understand how regeneration proceeds successfully in nature. In particular, we are interested in how a planarian regenerates its central nervous system (CNS), making new neurons and connecting them faithfully again and again.
You can see in the images above what our planarians look like. They have a central nervous system (CNS) that is diagrammed in the middle; the CNS controls many behaviors that include feeding, avoidance of light, response to touch/vibration, and mating. The image on the right shows the expression of a gene that is present in neurons that signal with small proteins called neuropeptides.
The amazing regenerative ability of planarians is shown here. In the top images, a the head of a planarian was removed, leaving only the tail. This animal was imaged right away (0 days) and each day after amputation. The new head appears gradually and initially lacks brown pigment. The eyes appear in only one week (7 days). In the bottom panels, you can see what's going on inside the regenerating head. New neurons appear after 3 days (arrow). By 5 days after amputation, the "horseshoe" shape of the planarian brain has returned and the green signal is visible as neurons resume their connections with one another.
Our ongoing work:
To understand how planarians successfully regenerate the CNS, we are currently pursuing projects to answer the following questions:
What signals promote planarian regeneration, both generally and specifically for the CNS? Does the CNS send signals to promote regeneration? How does the anterior pole direct brain formation and/or neurogenesis?
What local environments/signals influence stem cell behaviors? How are stem cells triggered to become neurons?
How are new neurons arranged properly in space and how do they make the correct connections with their partners? How is neural diversity reestablished after injury? How are different elements of the nervous system (e.g. central vs. peripheral nervous system) reestablished?
How are glial cells in the nervous system regenerated? And what role(s), if any, do they play in the regeneration of the CNS?
Project 5 (undergrads in the lab)
Most undergraduate students in the lab work to identify and characterize new genes that are important for aspects of regeneration and/or neurobiology. Current projects focus on a transcription factor-encoding gene and a group of extracellular proteins that share the laminin G domain. We are also working with first-year CURE students in the Cell and Molecular Biology program at Grand Valley State University to identify cell cycle regulators important for planarian stem cell biology.