journal article Open Access Sep 14, 2023

Ets-1 transcription factor regulates glial cell regeneration and function in planarians

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Abstract
ABSTRACT
Glia play multifaceted roles in nervous systems in response to injury. Depending on the species, extent of injury and glial cell type in question, glia can help or hinder the regeneration of neurons. Studying glia in the context of successful regeneration could reveal features of pro-regenerative glia that could be exploited for new human therapies. Planarian flatworms completely regenerate their nervous systems after injury – including glia – and thus provide a strong model system for exploring glia in the context of regeneration. Here, we report that planarian glia regenerate after neurons, and that neurons are required for correct glial numbers and localization during regeneration. We also identify the planarian transcription factor-encoding gene ets-1 as a key regulator of glial cell maintenance and regeneration. Using ets-1 (RNAi) to perturb glia, we show that glial loss is associated with altered neuronal gene expression, impeded animal movement and impaired nervous system architecture – particularly within the neuropil. Importantly, our work reveals the inter-relationships of glia and neurons in the context of robust neural regeneration.
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References
111
[1]
The diversity and disparity of the glial scar

Katrina L. Adams, Vittorio Gallo

Nature Neuroscience 2018 10.1038/s41593-017-0033-9
[2]
Aldskogius "Central neuron–glial and glial–glial interactions following axon injury" Prog. Neurobiol. (1998) 10.1016/s0301-0082(97)00093-2
[3]
Alesci "Neuronal regeneration: vertebrates comparative overview and new perspectives for neurodegenerative diseases" Acta Zool. (2022) 10.1111/azo.12397
[4]
Glia as architects of central nervous system formation and function

Nicola J. Allen, David A. Lyons

Science 2018 10.1126/science.aat0473
[5]
Amouyel "Expression of ETS proto-oncogenes in astrocytes in human cortex" Brain Res. (1988) 10.1016/0006-8993(88)90976-6
[6]
Anderson "Astrocyte scar formation aids central nervous system axon regeneration" Nature (2016) 10.1038/nature17623
[7]
Anthony "Radial Glia serve as neuronal progenitors in all regions of the central nervous system" Neuron (2004) 10.1016/s0896-6273(04)00140-0
[8]
Araque "Tripartite synapses: Glia, the unacknowledged partner" Trends Neurosci. (1999) 10.1016/s0166-2236(98)01349-6
[9]
c-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration

Peter J. Arthur-Farraj, Morwena Latouche, Daniel K. Wilton et al.

Neuron 2012 10.1016/j.neuron.2012.06.021
[10]
Barnabé-Heider "Evidence that embryonic neurons regulate the onset of cortical gliogenesis via Cardiotrophin-1" Neuron (2005) 10.1016/j.neuron.2005.08.037
[11]
Bayraktar "Combinatorial temporal patterning in progenitors expands neural diversity" Nature (2013) 10.1038/nature12266
[12]
Burda "Reactive gliosis and the multicellular response to CNS damage and disease" Neuron (2014) 10.1016/j.neuron.2013.12.034
[13]
Campbell "Radial glia: multi-purpose cells for vertebrate brain development" Trends Neurosci. (2002) 10.1016/s0166-2236(02)02156-2
[14]
Cebrià "Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture" Development (2005) 10.1242/dev.01941
[15]
Cebrià "FGFR-related gene nou-darake restricts brain tissues to the head region of planarians" Nature (2002) 10.1038/nature01042
[16]
Dissecting planarian central nervous system regeneration by the expression of neural‐specific genes

Francesc Cebrià, Masumi Nakazawa, Katsuhiko Mineta et al.

Development, Growth & Differentiation 2002 10.1046/j.1440-169x.2002.00629.x
[17]
Chen "Isolation and characterization of five Drosophila genes that encode an ets-related DNA binding domain" Dev. Biol. (1992) 10.1016/0012-1606(92)90225-6
[18]
Collins "Genome-wide analyses reveal a role for peptide hormones in planarian germline development" PLoS Biol. (2010) 10.1371/journal.pbio.1000509
[19]
Coutinho-Budd "The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function" Genes Dev. (2017) 10.1101/gad.305888.117
[20]
Cowles "Genome-wide analysis of the bHLH gene family in planarians identifies factors required for adult neurogenesis and neuronal regeneration" Development (2013) 10.1242/dev.098616
[21]
Cowles "COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians" PLoS Genet. (2014) 10.1371/journal.pgen.1004746
[22]
Crews "Drosophila embryonic CNS development: neurogenesis, gliogenesis, cell fate, and differentiation" Genetics (2019) 10.1534/genetics.119.300974
[23]
Currie "Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain" eLife (2016) 10.7554/elife.19735
[24]
Davies "Embryonic origin of adult stem cells required for tissue homeostasis and regeneration" eLife (2017) 10.7554/elife.21052
[25]
Phylogeny.fr: robust phylogenetic analysis for the non-specialist

A. Dereeper, V. Guignon, G. Blanc et al.

Nucleic Acids Research 2008 10.1093/nar/gkn180
[26]
Doherty "Ensheathing glia function as phagocytes in the adult Drosophila brain" J. Neurosci. (2009) 10.1523/jneurosci.5951-08.2009
[27]
Dubey "S. mediterranea ETS-1 regulates the function of cathepsin-positive cells and the epidermal lineage landscape via basement membrane remodeling" J. Cell Sci. (2022) 10.1242/jcs.259900
[28]
Ebens "The Drosophila anachronism locus: a glycoprotein secreted by glia inhibits neuroblast proliferation" Cell (1993) 10.1016/0092-8674(93)90291-w
[29]
MUSCLE: multiple sequence alignment with high accuracy and high throughput

R. C. Edgar

Nucleic Acids Research 2004 10.1093/nar/gkh340
[30]
Eroglu "Regulation of synaptic connectivity by glia" Nature (2010) 10.1038/nature09612
[31]
Reactive astrocyte nomenclature, definitions, and future directions

Carole Escartin, Elena Galea, András Lakatos et al.

Nature Neuroscience 2021 10.1038/s41593-020-00783-4
[32]
Falk "Glial control of neurogenesis" Curr. Opin. Neurobiol. (2017) 10.1016/j.conb.2017.10.025
[33]
Fincher "Cell type transcriptome atlas for the planarian Schmidtea mediterranea" Science (2018) 10.1126/science.aaq1736
[34]
Fleischman "ets-1 in astrocytes: Expression and transmitter-evoked phosphorylation" Mol. Cell. Biol. (1995) 10.1128/mcb.15.2.925
[35]
Fraguas "Regeneration of neuronal cell types in Schmidtea mediterranea: an immunohistochemical and expression study" Int. J. Dev. Biol. (2012) 10.1387/ijdb.113428sf
[36]
Gallo "Glial development: the crossroads of regeneration and repair in the CNS" Neuron (2014) 10.1016/j.neuron.2014.06.010
[37]
ExPASy: the proteomics server for in-depth protein knowledge and analysis

E. Gasteiger

Nucleic Acids Research 2003 10.1093/nar/gkg563
[38]
Goldshmit "Fgf-dependent glial cell bridges facilitate spinal cord regeneration in Zebrafish" J. Neurosci. (2012) 10.1523/jneurosci.0758-12.2012
[39]
New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0

Stéphane Guindon, Jean-François Dufayard, Vincent Lefort et al.

Systematic Biology 2010 10.1093/sysbio/syq010
[40]
Hagedorn "The Ets domain transcription factor erm distinguishes rat satellite glia from schwann cells and is regulated in satellite cells by neuregulin signaling" Dev. Biol. (2000) 10.1006/dbio.1999.9595
[41]
Hartline "The evolutionary origins of glia" Glia (2011) 10.1002/glia.21149
[42]
He "FOX and ETS family transcription factors regulate the pigment cell lineage in planarians" Development (2017) 10.1242/dev.156349
[43]
Hidalgo "Targeted ablation of glia disrupts axon tract formation in the Drosophila CNS" Development (1995) 10.1242/dev.121.11.3703
[44]
Inoue "Morphological and functional recovery of the planarian photosensing system during head regeneration" Zoolog. Sci. (2004) 10.2108/zsj.21.275
[45]
Jäkel "Glial cells and their function in the adult brain: a journey through the history of their ablation" Front. Cell. Neurosci. (2017) 10.3389/fncel.2017.00024
[46]
Jenkins "Heterotrimeric G proteins regulate planarian regeneration and behavior" Genetics (2023) 10.1093/genetics/iyad019
[47]
Jessen "Glial cells" Int. J. Biochem. Cell Biol. (2004) 10.1016/j.biocel.2004.02.023
[48]
The repair Schwann cell and its function in regenerating nerves

K. R. Jessen, R. Mirsky

The Journal of Physiology 2016 10.1113/jp270874
[49]
Jung "Phagocytic roles of Glial cells in healthy and diseased brains" Biomolecul. Ther. (2018) 10.4062/biomolther.2017.133
[50]
King "In situ hybridization protocol for enhanced detection of gene expression in the planarian Schmidtea mediterranea" BMC Dev. Biol. (2013) 10.1186/1471-213x-13-8

Showing 50 of 111 references

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Citations
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References
Details
Published
Sep 14, 2023
Vol/Issue
150(18)
License
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Funding
National Cancer Institute
National Institutes of Health Award: ZIABC0120009
Alfred P. Sloan Foundation
McKnight Foundation
University of Georgia
Cite This Article
Bidushi Chandra, Matthew G. Voas, Erin L. Davies, et al. (2023). Ets-1 transcription factor regulates glial cell regeneration and function in planarians. Development, 150(18). https://doi.org/10.1242/dev.201666
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