Biology subjects

Taylor, O.

Publications and source records attributed to Taylor, O..

5 recordsLinked to original sources

bioRxiv2025

Sphingosine-1-phosphate signaling through Müller glia regulates neuroprotection and the accumulation of immune cells in the rodent retina

The purpose of this study was to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, neuroprotection, and reprogramming of Muller glia (MG) into neurogenic MG-derived progenitor cells (MGPCs) in the adult mouse retina. We found that S1P-related genes were dynamically regulated following retinal damage. S1pr1 (encoding S1P receptor 1) and Sphk1 (encoding sphingosine kinase 1) are expressed at low levels by resting MG and are rapidly upregulated following acute damage. Overexpression of the neurogenic bHLH transcription factor Ascl1 in MG downregulates S1pr1, and inhibition of Sphk1 and S1pr1/3 enhances Ascl1-driven differentiation of bipolar-like cells and suppresses glial differentiation. Treatments that activate S1pr1 or increase retinal levels of S1P initiate pro-inflammatory NF{kappa}B-signaling in MG, whereas treatments that inhibit S1pr1 or decreased levels of S1P suppress NF{kappa}B-signaling in MG in damaged retinas. Conditional knock-out of NF{kappa}B-signaling in MG increases glial expression of S1pr1 but decreases levels of S1pr3 and Sphk1. Conditional knock-out (cKO) of S1pr1 in MG, but not Sphk1, enhances the accumulation of immune cells in acutely damaged retinas. cKO of S1pr1 is neuroprotective to ganglion cells, whereas cKO of Sphk1 is neuroprotective to amacrine cells in NMDA-damaged retinas. Consistent with these findings, pharmacological treatments that inhibit S1P receptors or inhibit Sphk1 had protective effects upon inner retinal neurons. We conclude that the S1P-signaling pathway is activated in MG after damage and this pathway acts secondarily to restrict the accumulation of immune cells, impairs neuron survival and suppresses the reprogramming of MG into neurogenic progenitors in the adult mouse retina.

neuroscience↗

bioRxiv2024

Extending sampling approaches for great crested newt (Triturus cristatus) eDNA monitoring

O_LIEnvironmental DNA (eDNA) monitoring has been used for great crested newt (Triturus cristatus) survey in the UK since the publication of a Defra-funded trial in 2014. If eDNA results are to be used in support of a great crested newt licence, surveys must be performed during a 76-day survey window (15 April - 30 June) to coincide with peak great crested newt activity, and must follow the approved ethanol precipitation protocol. However, eDNA detection is possible in other months and filtration may be a more effective method of eDNA capture. C_LIO_LIWe investigated whether the great crested newt eDNA survey season could be extended and filtration could be used for great crested newt eDNA capture by reviewing the available evidence and conducting a field study from April to October 2022. Paired water samples for ethanol precipitation and filtration were collected from 25 ponds once a month, resulting in 124 samples of each type. All samples (N = 248) were analysed with the approved great crested newt quantitative PCR assay. C_LIO_LIOur results indicate that great crested newts can be reliably detected using both eDNA capture methods from April to August, with detection rates decreasing in September and October. Great crested newt eDNA detection was comparable or higher with filtration than ethanol precipitation. C_LIO_LIPractical implication. Acceptance of filtration for great crested newt eDNA surveys could allow more water to be processed for robust and reliable estimates of great crested newt presence. Extending the great crested newt eDNA survey season to August could allow more waterbodies to be surveyed for great crested newt presence (but not absence), and identification of sites that provide important habitat for great crested newts outside of the breeding season. This would also remove logistical challenges and costs associated with completing sampling within 11 weeks and laboratory analysis within 10 working days from sample receipt. Furthermore, great crested newt eDNA surveys could be more frequently carried out alongside monitoring for other species, which are typically surveyed from April to September/October or year-round with conventional methods or eDNA surveys using filtration. This could enable infrastructure projects to develop more effective mitigation measures as well as reduce time required from surveyors and survey costs. C_LI

ecology↗

bioRxiv2024

Sphingosine-1-phosphate signaling regulates the ability of Müller glia to become neurogenic, proliferating progenitor-like cells

The purpose of these studies is to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, dedifferentiation of Muller glia (MG), reprogramming into proliferating MG-derived progenitor cells (MGPCs), and neuronal differentiation of the progeny of MGPCs in the chick retina. We found that S1P-related genes are highly expressed by retinal neurons and glia, and levels of expression were dynamically regulated following retinal damage. Drug treatments that activate S1P receptor 1 (S1PR1) or increase levels of S1P suppressed the formation of MGPCs. Conversely, treatments that inhibit S1PR1 or decrease levels of S1P stimulated the formation of MGPCs. Inhibition of S1P receptors or S1P synthesis significantly enhanced the neuronal differentiation of the progeny of MGPCs. We report that S1P-related gene expression in MG is modulated by microglia and inhibition of S1P receptors or S1P synthesis partially rescues the loss of MGPC formation in damaged retinas missing microglia. Finally, we show that TGF{beta}/Smad3 signaling in the resting retina maintains S1PR1 expression in MG. We conclude that the S1P signaling is dynamically regulated in MG and MGPCs in the chick retina, and activation of S1P signaling depends, in part, on signals produced by reactive microglia.

neuroscience↗

bioRxiv2023

Transglobal spread of an ecologically significant sea urchin parasite

Mass mortality of the dominant coral reef herbivore Diadema antillarum in the Caribbean in the early 1980s led to a persistent phase shift from coral-to algal-dominated reefs. In 2022, a scuticociliate most closely related to Philaster apodigitiformis caused further mass mortality of D. antillarum across the Caribbean, leading to >95% mortality at affected sites. Mortality was also reported in the related species Diadema setosum in the Mediterranean in 2022, where urchins experienced gross signs compatible with scuticociliatosis. However, the causative agent of the Mediterranean outbreak has not yet been determined. In April 2023, mass mortality of D. setosum occurred along the Sultanate of Omans coastline. Urchins displayed signs compatible with scuticociliatosis including abnormal behavior, drooping and loss of spines, followed by tissue necrosis and death. Here we report the detection of an 18S rRNA gene sequence in abnormal urchins from Muscat, Oman that is identical to the Philaster strain responsible for D. antillarum mass mortality in the Caribbean. We also show that scuticociliatosis signs can be elicited in D. setosum by experimental challenge with the cultivated Philaster strain associated with Caribbean scuticociliatosis. These results demonstrate the Philaster sp. associated with D. antillarum mass mortality has rapidly spread to geographically distant coral reefs, compelling global-scale awareness and monitoring for this devastating condition through field surveys, microscopy, and molecular microbiological approaches, and prompting investigation of long-range transmission mechanisms.

ecology↗

bioRxiv2023

ID transcription factors regulate the ability of Muller glia to become proliferating neurogenic progenitor-like cells

The purpose of this study was to investigate how ID transcription factors (TFs) regulate the ability of Muller glia (MG) to reprogram into proliferating MG-derived progenitor cells (MGPCs) in the chick retina. We found that ID1 is transiently expressed by maturing MG, whereas ID4 is upregulated and maintained in maturing MG in embryonic retinas. In mature retinas, ID4 was prominently expressed by resting MG, but in response to retinal damage ID4 was rapidly upregulated and then downregulated in MGPCs. By contrast, ID1, ID2 and ID3 were low in resting MG and then upregulated by MGPCs. Inhibition of ID TFs following retinal damage decreased numbers of proliferating MGPCs. Inhibition of IDs after the proliferation of MGPCs significantly increased numbers of progeny that differentiate as neurons. In damaged or undamaged retinas inhibition of IDs increased levels of p21Cip1 in MG. In response to damage or insulin+FGF2 levels of CDKN1A message and p21Cip1 protein were decreased, absent in proliferating MGPCs, and elevated in MG returning to a resting phenotype. Inhibition of Notch- or gp130/Jak/Stat-signaling in damaged retinas increased levels of ID4 but not p21Cip1 in MG. Although ID4 is the predominant isoform expressed by MG in the chick retina, id1 and id2a are predominantly expressed by resting MG and downregulated in activated MG and MGPCs in zebrafish retinas. We conclude that ID TFs have a significant impact on regulating the responses of MG to retinal damage, controlling the ability of MG to proliferate by regulating levels of p21Cip1, and suppressing the neurogenic potential of MGPCs.

neuroscience↗