This post is written by UW grad student Shawn Luttrell
One of the great marvels in biology is the ability to regenerate a fully functional nervous system after damage from disease or injury. Scientists have studied this remarkable process for decades, but it is still largely a mystery how some animals accomplish this incredible feat. Humans have limited regenerative abilities, particularly in the central nervous system (CNS; Chernoff et al., 2002; Poss, 2010; Stocum, 2006). Some peripheral neurons can regenerate to a certain degree however, damage to the brain or spinal cord usually results in permanent, catastrophic impediments that are not corrected though regenerative mechanisms (Yannas IV, 2001). Animal models that are capable of extensive and complete nervous system regeneration are needed to effectively make strides in understanding the molecular mechanisms underlying this trait. Moreover, models that are closely related to humans will likely provide greater insight to achieving extensive mammalian CNS regeneration as many of the same genes, gene networks, and developmental programs are shared between the deuterostomes (Figure 1; Davidson and Erwin, 2006; Swalla, 2006).
I am a fifth year graduate student in the Swalla lab in the Biology Department at the University of Washington and I am defending my Ph.D. at the end of this month. I have focused my dissertation research on CNS regeneration in the solitary hemichordate, Ptychodera flava. This animal is also known as an acorn worm and is closely related to echinoderms, like sea stars and sea urchins. Hemichordates are strictly marine animals and all acorn worms have a tripartite body plan with anterior proboscis that is used for digging and burrowing in the sand and mud, a middle collar region, a ventral mouth between the proboscis and collar, and a long posterior trunk (Figure 2). Hemichordates are in the same group of animals as chordates, including humans, and as such, share numerous developmental and morphological features (Figure 1). Most notably for my research, P. flava has a hollow, dorsal neural tube in the collar region that our lab has shown develops in a very similar fashion to the chordate neural tube (Luttrell et al., 2012). In humans, the neural tube becomes the brain and spinal cord. More impressive is the fact that P. flava can regenerate its neural tube after complete ablation. In fact, they can regenerate all of their body structures (Figure 3; Humphreys et al., 2010; Luttrell et al., 2016; Rychel and Swalla, 2008).
The first two chapters of my dissertation are published on chordate evolution and hemichordate regeneration (Luttrell and Swalla, 2014; Luttrell et al., 2016). We detailed the regeneration transcriptome for anterior regeneration in adult P. flava worms. This showed all of the genes that are turned on or off controlling the regeneration process. Now we know nearly a thousand genes involved with hemichordate regeneration and we are investigating which of these genes are actually required for regeneration and which genes play a support role. The second chapter also details the internal regeneration morphology, so we know when structures and organs regenerate in hemichordates and from what tissues they are derived. We compared this temporal and spatial regeneration data to early development and found there are differences between the way certain structures regenerate and the way they are originally made when P. flava larvae metamorphose into adult worms.
Ptychodera flava begins life as a planktonic, feeding, tornaria larva that can remain in the water column for up to three hundred days (Figure 4; Hadfield, 1978). It had not been determined, however, at what point during development the regeneration program is activated. It may have been that regeneration is initiated after the animal undergoes metamorphosis from a planktonic larva into a juvenile worm or it may be that the regeneration program becomes active at some point before metamorphosis. The final chapter of my dissertation investigates these questions, and I have shown that P. flava larvae are also able to extensively regenerate. This is important because functional studies aimed at uncovering the genetic and molecular mechanisms controlling the regeneration process may, in certain cases, be more tractable in the larvae due to their small size, transparency, and relatively simple body plan and tissues compared to adults acorn worms. Even though P. flava larvae do not possess a neural tube pre-metamorphosis, the regeneration program is likely the same for both larvae and adults. This final chapter of my dissertation is now complete and will soon be submitted for publication. Many of these studies benefited from BEACON funding. In particular, BEACON funded the last two quarters of my graduate studies, which allowed me to gather most of the data for this chapter and finalize my dissertation. I will start Postdoctoral studies at ISCRM (The Institute of Stem Cell and Regenerative Medicine in Seattle in August, continuing to study regeneration and evolution in action! Thank you BEACON!!
Chernoff EA, Sato K, Corn A, Karcavich RE. (2002). Spinal cord regeneration: intrinsic properties and emerging mechanisms. Semin Cell Dev Biol. 13(5): 361-368.
Davidson EH, Erwin DH. (2006). Gene regulatory networks and the evolution of animal body plans. Science. 311: 796-800.
Hadfield MG. (1978). Growth and metamorphosis of planktonic larvae of Ptychodera flava (Hemichordata: Enteropneusta). In: Chia FS, Rice ME, editors. Settlement and metamorphosis of marine invertebrate larvae. New York: Elsevier. p 247–254.
Humphreys, T., Sasaki, A., Uenishi, G., Taparra, K., Arimoto, A,. Tagawa, K. (2010). Regeneration in the hemichordate Ptychodera flava. Zoolog Sci. 27(2), 91-95.
Luttrell S, Konikoff C, Byrne A, Bengtsson B, Swalla B. (2012) Ptychoderid hemichordate neurulation without a notochord. Integr Comp Biol. 52(6): 829-34.
Luttrell SM, Gotting K, Ross E, Alvarado AS, Swalla BJ. (2016). Head regeneration in hemichordates is not a strict recapitulation of development. Dev Dynamics 245: 1159-1175.
Luttrell SM and Swalla BJ. (2014). Genomic and Evolutionary Insights into Chordate Origins. In “Principles of Developmental Genetics”, 2nd edition. Sally Moody, ed. (Elsevier, San Diego.) pp. 116-126.
Poss KD. (2010). Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 11: 710–722.
Rychel, A.L. and Swalla, B.J. (2008). Anterior regeneration in the hemichordate Ptychodera flava. Dev. Dyn. 237(11), 3222-3232.
Stocum D. (2006). Regenerative Biology and Medicine. London: Academic Press.
Swalla BJ. (2006). Building divergent body plans with similar genetic pathways. Heredity 97: 235-243.
Yannas IV (2001) Tissue and organ regeneration in adults. Springer-Verlag New York, Inc. pp. 138–185.