HomeBiologyA regeneration retrospective: go fish

A regeneration retrospective: go fish

First, I’d be remiss to not acknowledge that almost all of my posts have been on vertebrate programs when many invertebrates are additionally studied for his or her regenerative capability. One such instance is Hydra (Vogg et al., 2019) however Hydra papers don’t appear to seem in JEEM/Growth till the Nineteen Sixties. Whereas exploring the early problems with JEEM/Growth, I discovered fish manuscripts have been equally uncommon, which is shocking as a result of – right now – zebrafish are a outstanding mannequin for improvement and regeneration (Marques et al., 2019). Certainly, there was additionally a notable absence of any research of nervous system regeneration, perhaps as a result of such articles have been submitted to extra specialist neurobiology and neuroscience journals. On this ultimate publish of the sequence, we fill this lacking hyperlink by discussing the highlights from the next articles:


Caltech researcher Roger Wolcott Sperry is most well-known for his work on the ‘cut up mind speculation’ and the corpus callosum, for which he received the Nobel Prize for Drugs/Physiology in 1981 (Hubel, 1994; De León Reyes et al., 2020). Alongside his work in cats, Sperry printed just a few articles on cichlid fish. One such article was printed in JEEM/Growth in 1957 (Arora and Sperry, 1967). His colleague, R. W. Arora, appears to have left little hint however I believe it’s doubtless he introduced the fish to the entire operation. Their examine continued earlier work on the premise that people did not regenerate motor neurons due to aberrant steering and muscle innervation following wounding or amputation, which doesn’t happen in different vertebrates. To study extra about peripheral nervous system (Murtazina and Adameyko, 2023) regeneration, Arora and Sperry centered on the mandible of Astronotus ocellatus, severing the left mandibular nerve of ten fish and inflicting partial paralysis had fully recovered by 16 days post-operation (Fig. 1, left). Subsequent, they lower the person branches of the mandibular nerve and crossed them in order that the nerves lay subsequent to muscle mass they wouldn’t usually innervate (Fig. 1, proper). General, as with the whole nerve cuts, mandible operate was recovered a few weeks later with the nerves innervating the adjoining muscle somewhat than their unique goal (I’ve simplified the outcomes right here, do see the manuscript for full particulars). Arora and Sperry even used an electrical induction coil to show innovation and present that stimulating the regenerated nerves would trigger the contraction of the brand new muscle goal. This work confirmed the plasticity of the peripheral nervous system to adapt to the rewiring of the motor neurons with new muscle mass. Moreover, this examine confirmed that the steering cues that direct motor neuron migration and innovation throughout improvement won’t be current throughout regeneration, signalling the significance of the microenvironment for pathfinding and differentiating the necessities for neuronal concentrating on vs. neuronal innervation.


Fig. 1. Left: “Sketch of jaw musculature and its innervation in Astronotus ocellatus. The 2 superficial adductor muscle mass are lower and deflected to reveal the deeper adductor muscle. Arrows point out level of part of mandibularis V nerve in Sequence I.” Proper “Sketch exhibiting cross-union of levator and depressor branches of mandibularis V nerve.” Taken from Arora and Sperry, 1957.

Teleost fish, together with cichlids, are outstanding in right now’s analysis, though I believe it’s truthful to say that zebrafish are a dominant system. The explosion of zebrafish research can largely be attributed to the Boston and Tübingen screens, culminating within the publication of a particular problem of Growth somewhat over 25 years in the past (Nüsslein-Volhard 2012; Mullins et al., 2019). Since, the technology of a whole lot (extra?) of genetic strains, together with fluorescent genetic reporters that capitalise on the zebrafish’s amenability to microscopy and imaging. As with cardiac regeneration, which we heard about earlier this week, the zebrafish (in contrast to most mammals, together with people) can regenerate its spinal twine (Becker and Becker, 2022).


Along with the peripheral nervous system, zebrafish have a exceptional capability for regenerating the central nervous system, together with the spinal twine, following harm – a phenomenon that doesn’t happen in mammals as a consequence of glial cell-dependent scarring. Thus, understanding the right way to forestall scaring and/or induce regeneration has large therapeutic potential for spinal twine accidents. Of their latest Growth paper, Zhou and colleagues use a set of refined genetic instruments to ask how glial cells reply to harm in zebrafish (Zhou et al., 2023). The authors first generate ctgfa-Tracer zebrafish for lineage tracing ctgfa-expressing cells, similar to bridging glia, which emerge following spinal twine harm. Utilizing this line, the authors present that bridging glia, ventral ependymal progenitors and regenerating glial cells are derived from ctfga-expressing cells however they minimally contribute to neurons and oligodendrocytes. The authors subsequent flip to ctfga regulation, revealing the gene-regulatory sequences that drive ctfga expression throughout regeneration. Lastly, the authors particularly ablate ctgfa-expressing cells, and present that axon outgrowth and swimming behaviour are affected following spinal harm. Collectively, Zhou and colleagues decide that ctfga-expressing cells have a pro-regenerative function in spinal twine regeneration.

Fig. 2. “A distal enhancer component directs glial ctgfa expression after SCI.” Taken from Fig. 4B (Zhou et al., 2023). Please see the unique publication for the total legend.

Each these papers handle the power of teleost fish to regenerate the nervous system and spotlight the significance of the native microenvironment, in addition to utilizing animal behaviour (e.g. consuming and swimming) as a read-out of phenotype. Arora and Sperry confirmed the regenerative plasticity of the peripheral nervous system, whereas Zhou and colleagues highlighted a specific cell inhabitants that helps and contributes to central nervous system regeneration.

I hope this little sequence has been entertaining – I’ve actually loved studying extra about these early papers and the researchers who wrote them. Would you be fascinated by studying extra ‘every now and then’ or ‘previous and current’ posts on different subjects? Share your ideas within the feedback.


H. L. Arora, R. W. Sperry; Myotypic Respecification of Regenerated Nerve-fibres in Cichlid Fishes. Growth 1 September 1957; 5 (3): 256–263. doi: https://doi.org/10.1242/dev.5.3.256

Thomas Becker, Catherina G. Becker; Regenerative neurogenesis: the combination of developmental, physiological and immune alerts. Growth 15 April 2022; 149 (8): dev199907. doi: https://doi.org/10.1242/dev.199907

D. Hubel; Roger W. Sperry (1913–1994). Nature 369, 1994; 186. https://doi.org/10.1038/369186a0

Noelia S. De León Reyes, Lorena Bragg-Gonzalo, Marta Nieto; Growth and plasticity of the corpus callosum. Growth 15 September 2020; 147 (18): dev189738. doi: https://doi.org/10.1242/dev.189738

Ines J. Marques, Eleonora Lupi, Nadia Mercader; Mannequin programs for regeneration: zebrafish. Growth 15 September 2019; 146 (18): dev167692. doi: https://doi.org/10.1242/dev.167692

Mary C. Mullins, Joaquín Navajas Acedo, Rashmi Priya, Lilianna Solnica-Krezel, Stephen W. Wilson; The zebrafish problem: 25 years on. Growth 15 December 2021; 148 (24): dev200343. doi: https://doi.org/10.1242/dev.200343

Aliia Murtazina, Igor Adameyko; The peripheral nervous system. Growth 1 Could 2023; 150 (9): dev201164. doi: https://doi.org/10.1242/dev.201164

Christiane Nüsslein-Volhard; The zebrafish problem of GrowthGrowth 15 November 2012; 139 (22): 4099–4103. doi: https://doi.org/10.1242/dev.085217

Stefano Sandrone. Roger W. Sperry (1913-1994). J Neurol. 2022 Sep;269(9):5194-5195. doi: 10.1007/s00415-022-11232-6. Epub 2022 Jul 22. PMID: 35867150; PMCID: PMC9363358.

Matthias C. Vogg, Brigitte Galliot, Charisios D. Tsiairis; Mannequin programs for regeneration: HydraGrowth 1 November 2019; 146 (21): dev177212. doi: https://doi.org/10.1242/dev.177212

Lili Zhou, Anthony R. McAdow, Hunter Yamada, Brooke Burris, Dana Klatt Shaw, Kelsey Oonk, Kenneth D. Poss, Mayssa H. Mokalled; Progenitor-derived glia are required for spinal twine regeneration in zebrafish. Growth 15 Could 2023; 150 (10): dev201162. doi: https://doi.org/10.1242/dev.201162

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