Ravanelli AM, Appel B. Motor neurons and oligodendrocytes arise from distinct cell lineages by progenitor recruitment. Genes Dev. 2015 Dec 1;29(23):2504-15. doi: 10.1101/gad.271312.115. Epub 2015 Nov 19. PMID: 26584621; PMCID: PMC4691953.
This work, performed by Dr. Andy Ravanelli as a postdoctoral fellow, provided our first evidence, drawn from elegant fate mapping experiments, that motor neurons and oligodendrocytes arise from distinct subpopulations of spinal cord progenitor cells, rather than from common progenitors. Read the paper. |
Scott K, O'Rourke R, Winkler CC, Kearns CA, Appel B. Temporal single-cell transcriptomes of zebrafish spinal cord pMN progenitors reveal distinct neuronal and glial progenitor populations. Dev Biol. 2021 Nov;479:37-50. doi: 10.1016/j.ydbio.2021.07.010. Epub 2021 Jul 23. PMID: 34303700; PMCID: PMC8410680.
This manuscript was the work of Dr. Kayt Scott, who was at the time a CSD graduate student, with a lot of help from Becky O'Rourke, our Section bioinformatics specialist, and Dr. Caitlin Winkler, a RNA Bioscience fellow. A true "pandemic project", Kayt pored her energy into learning bioinformatics and analyzing scRNA-seq data that we had produced a couple years earlier thanks to a RBI pilot project award. Amazingly, the data revealed a subpopulation of progenitors, which we called pre-OPCs, that appeared to be specified for oligodendrocyte and not neuronal fates, exactly corresponding to the progenitors that Andy Ravanelli had identified by fate mapping. Read the paper. |
Kirby BB, Takada N, Latimer AJ, Shin J, Carney TJ, Kelsh RN, Appel B. In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development. Nat Neurosci. 2006 Dec;9(12):1506-11. doi: 10.1038/nn1803. Epub 2006 Nov 12. PMID: 17099706.
This is where our work on oligodendrocytes really started. We had been making transgenic reporter lines for our fate specification work and quickly realized that they revealed the amazing morphology and behavior of OPCs. This was very much a, "see the pretty cell, we have no idea about mechanism" sort of paper (those were the days!). Much of our current work tracks back to this paper. Read the paper. |
Hines JH, Ravanelli AM, Schwindt R, Scott EK, Appel B. Neuronal activity biases axon selection for myelination in vivo. Nat Neurosci. 2015 May;18(5):683-9. doi: 10.1038/nn.3992. Epub 2015 Apr 6. PMID: 25849987; PMCID: PMC4414883.
This was our first attempt to understand something about the basis of myelin plasticity in response to neural activity. Dr. Jake Hines, who was a postdoctoral fellow at the time, led this work to show axon vesicle secretion promotes the growth and stability of myelin sheaths on select axons. It was during this work that we began to think that synaptic-like mechanisms might mediate axo-glial interactions. Read the paper. |
Hughes AN, Appel B. Oligodendrocytes express synaptic proteins that modulate myelin sheath formation. Nat Commun. 2019 Sep 11;10(1):4125. doi: 10.1038/s41467-019-12059-y. PMID: 31511515; PMCID: PMC6739339.
Following on Jake Hines' paper, Dr. Alex Hughes, then a Neuroscience graduate student, hypothesized that canonical post-synaptic proteins expressed by oligodendrocytes mediate axon ensheathment. Her tests of this hypothesis produced our first evidence of molecular mechanisms that might mediate myelin plasticity. Read the paper. Yergert KM, Doll CA, O'Rouke R, Hines JH, Appel B. Identification of 3' UTR motifs required for mRNA localization to myelin sheaths in vivo. PLoS Biol. 2021 Jan 13;19(1):e3001053. doi: 10.1371/journal.pbio.3001053. PMID: 33439856; PMCID: PMC7837478.
How is the number, length, and thickness of individual myelin sheaths regulated? One possibility is that myelin formation and growth is regulated by mRNAs that are localized to and translated in nascent myelin sheaths. Dr. Katie Yergert, who was a Molecular Biology graduate student, tested this by investigating localization of candidate mRNAs in vivo. Her work set the stage for identifying mechanisms that mediate local control of myelin characteristics. Read the paper. |
Fedder-Semmes KN, Appel B. The Akt-mTOR Pathway Drives Myelin Sheath Growth by Regulating Cap-Dependent Translation. J Neurosci. 2021 Oct 13;41(41):8532-8544. doi: 10.1523/JNEUROSCI.0783-21.2021. Epub 2021 Sep 2. PMID: 34475201; PMCID: PMC8513705.
In this paper Dr. Karlie Fedder-Semmes, then a Neuroscience graduate student, connected mTor function, a well-known driver of myelination, to Cap-dependent translation control via translation initiation factors. This work was important because it helped define mRNA targets that might be regulated by mTor signaling to control myelin sheath characteristics. Read the paper. |
Hughes AN, Appel B. Microglia phagocytose myelin sheaths to modify developmental myelination. Nat Neurosci. 2020 Sep;23(9):1055-1066. doi: 10.1038/s41593-020-0654-2. Epub 2020 Jul 6. PMID: 32632287; PMCID: PMC7483351.
After her first paper on synaptic protein functions in oligodendrocytes Alex Hughes was looking for a new challenge. Following on observations that newly formed myelin sheaths sometimes disappear and inspired by work indicating that microglia prune synapses, Alex hypothesized that microglia phagocytose myelin sheaths during development. Her evidence supporting that hypothesis, published in this paper, has launched numerous projects that we are currently pursuing. Read the paper. |
Doll CA, Scott K, Appel B. Fmrp regulates oligodendrocyte lineage cell specification and differentiation. Glia. 2021 Oct;69(10):2349-2361. doi: 10.1002/glia.24041. Epub 2021 Jun 10. PMID: 34110049; PMCID: PMC8373694.
Individuals with Fragile X syndrome (FXS) have white matter deficits but the mechanisms by which Fmrp, an RNA binding protein disrupted in FXS, promotes myelination are not known. Dr. Caleb Doll, an Assistant Research Professor, has been investigating developmental functions of Fmrp using zebrafish. In this paper he presented evidence that absence of Fmrp alters specification and differentiation of oligodendrocyte lineage cells. Read the paper. |