Dynamics and variability of neuronal subtype responses during growth, degrowth, and regeneration

Havrilak, Jamie A.; Al-Shaer, Layla; Baban, Noor; Akinci, Nesli; Layden, Michael J.

Background We are interested in nervous system dynamics in adult and regenerating animals. Preliminary studies suggest that some species alter neuronal number to scale with changes in body size. Similarly, in some species regenerates resulting from wholebody axis regeneration are smaller than their pre-amputated parent, but they maintain the correct proportionality, suggesting that tissue and neuronal scaling also occurs in regenerates. The cell dynamics and responses of neuronal subtypes during nervous system regeneration, scaling, and whole-body axis regeneration are not well understood in any system. The cnidarian sea anemone Nematostella vectensis is capable of wholebody axis regeneration, and its transparent, “simple” body plan and the availability of fluorescent reporter transgenic lines allow neuronal subtypes to be tracked in vivo in adult and regenerating animals. A number of observations suggest this anemone is able to alter its size in responses to changes in feeding. We utilized the NvLWamide-like::mCherry neuronal subtype transgenic reporter line to determine the in vivo response of neuronal subtypes during growth, degrowth, and regeneration. Results Nematostella alters its size in response to caloric intake, and the nervous system responds by altering neuronal number to scale as the animal changes in size. Neuronal numbers in both the endodermal and ectodermal nerve nets decreased as animals shrunk, increased as they grew, and the changes were reversible. Whole-body axis regeneration resulted in regenerates that were smaller than their pre-amputated size, and the regenerated nerve nets were reduced in neuronal number. Different neuronal subtypes had several distinct responses during regeneration that included consistent, no, and conditional increases in number. Conditional responses were regulated, in part, by the size of the remnant fragment and the position of the amputation site. Regenerates and adults with reduced nerve nets displayed normal behaviors, indicating that the nerve net retains functionality as it scales. Conclusion These data suggest that the Nematostella nerve net is dynamic, capable of scaling with changes in body size, and that neuronal subtypes display differential regenerative responses, which we propose may be linked to the scale state of the regenerating animals.