Biology subjects

Enos, S. J.

Publications and source records attributed to Enos, S. J..

4 recordsLinked to original sources

bioRxiv2026

Diverse origins and transcriptional profiles of macrophages in a spinal lesion in zebrafish

The injury responses of tissue-resident macrophages in the CNS (microglia) and blood-derived macrophages (BDMs) play key roles in successful regeneration of the zebrafish spinal cord, but the origins and dynamic behaviours of these immune cells are not well characterized. Here, we find that microglia, labelled by the p2ry12:GFP reporter gene, migrate long-distance through neural tissue from the brain to the spinal lesion site, while BDMs, labelled by the mpeg1:mCherry reporter gene, migrate mainly from the caudal hematopoietic tissue to the lesion and back. Half of p2ry12:GFP-positive microglia co-express mpeg1:mCherry, while mpeg1:mCherry-positive BDMs are mostly p2ry12:GFP-negative. However, a BDM sub-population starts to express p2ry12:GFP in the lesion. This indicates heterogeneous and dynamic gene expression in macrophage populations. Gene expression profiling reveals several microglia-like and BDM-like clusters in the lesion with gene expression profiles related to proliferation, phagocytosis, pro- and anti-inflammatory phenotypes and distinct expression of regeneration-relevant genes. The most abundant cell cluster are densely-packed microglia-like cells in the lesion core, which express the novel marker g0s2, as well as phagocytosis-related genes. Hence, regenerative success of the zebrafish spinal cord is linked to a heterogeneous and dynamic response of microglia and BDM subpopulations.

neuroscience↗

bioRxiv2024

Wound closure after brain injury relies on force generation by microglia in zebrafish

Wound closure after a brain injury is critical for tissue restoration but this process is still not well characterised at the tissue level. We use live observation of wound closure in larval zebrafish after inflicting a stab wound to the brain. We demonstrate that the wound closes in the first 24 hours after injury by global tissue contraction. Microglia accumulation at the point of tissue convergence precedes wound closure and computational modelling of this process indicates that physical traction by microglia could lead to wound closure. Indeed, genetically or pharmacologically depleting microglia leads to defective tissue repair. Live observations indicate centripetal deformation of astrocytic processes contacted by migrating microglia. Severing such contacts leads to retraction of cellular processes, indicating tension. Weakening tension by disrupting the F-actin stabilising gene lcp1 in microglial cells, leads to failure of wound closure. Therefore, we propose a previously unidentified mechanism of brain repair in which microglia has an essential role in contracting spared tissue. Understanding the mechanical role of microglia will support advances in traumatic brain injury therapies Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=191 HEIGHT=200 SRC="FIGDIR/small/597300v3_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@112aorg.highwire.dtl.DTLVardef@6712c4org.highwire.dtl.DTLVardef@101179borg.highwire.dtl.DTLVardef@b4ecb6_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Material aging causes centrosome weakening and disassembly during mitotic exit

Centrosomes must resist microtubule-mediated forces for mitotic chromosome segregation. During mitotic exit, however, centrosomes are deformed and fractured by those same forces, which is a key step in centrosome disassembly. How the functional material properties of centrosomes change throughout the cell cycle, and how they are molecularly tuned remain unknown. Here, we used optically-induced flow perturbations to determine the molecular basis of centrosome strength and ductility in C. elegans embryos. We found that both properties declined sharply at anaphase onset, long before natural disassembly. This mechanical transition required PP2A phosphatase and correlated with inactivation of PLK-1 (Polo Kinase) and SPD-2 (Cep192). In vitro, PLK-1 and SPD-2 directly protected centrosome scaffolds from force-induced disassembly. Our results suggest that, prior to anaphase, PLK-1 and SPD-2 confer strength and ductility to the centrosome scaffold so that it can resist microtubule-pulling forces. In anaphase, centrosomes lose PLK-1 and SPD-2 and transition to a weak, brittle state that enables force-mediated centrosome disassembly.

cell biology↗

bioRxiv2017

Phosphatase PP2A and microtubule pulling forces disassemble centrosomes during mitotic exit

Centrosomes are major microtubule-nucleating organelles that facilitate chromosome segregation and cell division in metazoans. Centrosomes comprise centrioles that organize a micron-scale mass of protein called pericentriolar material (PCM) from which microtubules nucleate. During each cell cycle, PCM accumulates around centrioles through phosphorylation-mediated assembly of PCM scaffold proteins. During mitotic exit, PCM swiftly disassembles by an unknown mechanism. Here, we used Caenorhabditis elegans embryos to determine the mechanism and importance of PCM disassembly in dividing cells. We found that the phosphatase PP2A and its regulatory subunit SUR-6 (PP2ASUR-6), together with cortically directed microtubule pulling forces, actively disassemble PCM. In embryos depleted of these activities, [~]25% of PCM persisted from one cell cycle into the next, resulting in cytokinetic furrow ingression errors, excessive centrosome accumulation, and embryonic death. Purified PP2ASUR-6 could dephosphorylate the major PCM scaffold protein SPD-5 in vitro. Our data suggest that PCM disassembly occurs through a combination of dephosphorylation of PCM components and catastrophic rupture of the PCM scaffold.

cell biology↗