The Beane Lab

Stem Cells, Regeneration & Morphogenesis
in the age of Quantum Biology

Beane Lab planarian worm
Wound Epithelium

Wound Epithelium

F-actin (green) and nuclear (blue) staining reveals the morphology of the wound edge.

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Research Project 3

Neural Growth Termination

For obvious reasons, there is a lot of interest in how regeneration gets started. But have you ever thought about what gets it stopped?

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Control (on left) eye regeneration, and regeneration of excess of eyes (on right) following inhibition of PCP

Above: Control (on left) eye regeneration, and regeneration of excess of eyes (on right) following inhibition of PCP.

For obvious reasons, there is a lot of interest in how regeneration gets started. But have you ever thought about what gets it stopped? We have! Understanding the signals that stop new nerve growth will be important to coaxing our own central nervous system to renew after injury.

Our Research:

One of the largest black boxes in regeneration is how an organism decides when patterning is complete. A mechanism to stop regeneration must exist, since planarians do not keep regenerating new tissue indefinitely. But how this happens is unknown. Our data have revealed that for one tissue, specially the nervous system, the Planar Cell Polarity (PCP) pathway is required for the planarian nervous system to stop regenerating. Without PCP, the entire nervous system continues to grow for months after regeneration normally ends! Strikingly, the excess visual neurons produced result in regenerates that continually make new eyes.

We found that the restriction of neural growth by PCP is conserved in vertebrate regeneration and development, suggesting this is an ancestral role. Together the data reveal PCP inhibition may be a novel target for therapies aimed at initiating nerve regrowth in humans, where damage to the central nervous system is usually permanent. Our current goal is to determine which cells require PCP, how the PCP pathway interacts with stem cells to regulate neural progenitors, and how neural termination is integrated with the mechanisms that control the overall regeneration of shape. The ultimate aim is to identify therapeutic reagents for the initiation of neural regeneration.
Planarian nervous system showing commissural neurons with PCP inhibition showing excess neurons

Left: The planarian nervous system (in green), consists of a true brain, two ventral nerve cords that run the length of the body, and an intricate network of commissural and peripheral nerves. When PCP is inhibited, the regenerating worm regrows too many commissural neurons (yellow arrows).

Summary

While much attention has been paid to how neural growth is initiated after injury, our lab asks the opposite question: how does the regenerating nervous system know when to stop? We study the planar cell polarity (PCP) pathway's role in terminating neurogenesis.

Methods

Using RNAi to knock down PCP pathway components in planarians, combined with immunofluorescence for synapsin and other neural markers, we map the spatial and temporal regulation of neural growth termination.

Significance

Aberrant neural growth termination is implicated in neuropathic pain and neural tumors. Identifying stop signals could provide targets for conditions involving runaway neural growth.

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