Biology subjects

Kantarci, H.

Publications and source records attributed to Kantarci, H..

6 recordsLinked to original sources

bioRxiv2026

Actin disassembly triggers CNS myelin compaction and wrapping

Compact myelin enables rapid and precise impulse conduction in the vertebrate nervous system. During CNS development, oligodendrocytes wrap spirally around axons while compacting membranes, yet how cytoskeletal remodeling is coupled to these events remains unclear. Actin disassembly is required for wrapping, but whether wrapping is driven by iterative actin-based protrusion or follows a transition to actin-independent mechanisms is unresolved. Here we integrate tract-resolved developmental profiling, live-cell compaction mapping, and in vivo genetic perturbation to define how actin disassembly is coupled to myelin wrapping. We find that actin filaments undergo pronounced, sustained disassembly before active wrapping begins, with little evidence for persistent actin within sheaths during wrapping. We develop a live-cell assay that maps membrane compaction in cultured oligodendrocytes and show that compaction zones are depleted of actin filaments and expand when actin disassembly is promoted. Consistent with this model, oligodendrocyte-specific actin disassembly in vivo accelerates the appearance of thicker myelin early in development. Together, our results support a model in which actin disassembly promotes myelin wrapping by enabling membrane compaction, and provide a platform to dissect how compaction is regulated in development and disease.

neuroscience↗

bioRxiv2023

Oligodendrocyte calcium signaling regulates myelin sheath morphology

Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and can precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. Here, we used genetic tools to attenuate oligodendrocyte calcium signaling during active myelination in the developing mouse CNS. Surprisingly, we found that genetic calcium attenuation did not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation caused striking myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduced actin filaments in oligodendrocytes, and an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a novel cellular mechanism required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to sculpt myelin sheaths throughout the nervous system.

neuroscience↗

bioRxiv2022

Schwann cells promote sensory neuron excitability during development

Excitability--the ability to fire action potentials--is a signature feature of neurons. How neurons become excitable during development, and whether excitability is an intrinsic property of neurons or requires signaling from glial cells, remain unclear. Here we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of voltage-gated sodium channels and fire action potential trains. Inactivating this signaling pathway specifically in Schwann cells selectively impairs the maturation of nociceptor and proprioceptor somatosensory neuron subtypes, leading to corresponding sensory defects in thermoception, inflammatory pain, and proprioception. Our studies thus reveal a cell non-autonomous mechanism by which glia regulate neuronal excitability to enable the development of normal sensory functions.

neuroscience↗

bioRxiv2022

CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes

Myelin is required for rapid nerve signaling and is emerging as a key driver of CNS plasticity and disease. How myelin is built and remodeled remains a fundamental question of neurobiology. Central to myelination is the ability of oligodendrocytes to add vast amounts of new cell membrane, expanding their surface areas by many thousand-fold. However, how oligodendrocytes add new membrane to build or remodel myelin is unknown. Here, we show that CNS myelin membrane addition requires exocytosis mediated by the vesicular SNARE proteins VAMP2/3. Genetic inactivation of VAMP2/3 in myelinating oligodendrocytes caused severe hypomyelination and premature death without overt loss of oligodendrocytes. Through live imaging, we discovered that VAMP2/3-mediated exocytosis drives membrane expansion within myelin sheaths to initiate wrapping and power sheath elongation. In conjunction with membrane expansion, mass spectrometry of oligodendrocyte surface proteins revealed that VAMP2/3 incorporates axon-myelin adhesion proteins that are collectively required to form nodes of Ranvier. Together, our results demonstrate that VAMP2/3-mediated membrane expansion in oligodendrocytes is indispensable for myelin formation, uncovering a cellular pathway that could sculpt myelination patterns in response to activity-dependent signals or be therapeutically targeted to promote regeneration in disease.

neuroscience↗

bioRxiv2020

Label-free optical detection of bioelectric potentials using electrochromic thin films

Understanding how a network of interconnected neurons receives, stores, and processes information in the human brain is one of the outstanding scientific challenges of our time. The ability to reliably detect neuroelectric activities is essential to addressing this challenge. Optical recording using voltage-sensitive fluorescent probes has provided unprecedented flexibility for choosing regions of interest in recording neuronal activities. However, when recording at a high frame rate such as 500-1000 Hz, fluorescence-based voltage sensors often suffer from photobleaching and phototoxicity, which limit the recording duration. Here, we report a new approach, Electro-Chromic Optical REcording (ECORE), that achieves label-free optical recording of spontaneous neuroelectrical activities. ECORE utilizes the electrochromism of PEDOT:PSS thin films, whose optical absorption can be modulated by an applied voltage. Being based on optical reflection instead of fluorescence, ECORE offers the flexibility of an optical probe without suffering from photobleaching or phototoxicity. Using ECORE, we optically recorded spontaneous action potentials in cardiomyocytes, cultured hippocampal and dorsal root ganglion neurons, and brain slices. With minimal perturbation to cells, ECORE allows long-term optical recording over multiple days.

neuroscience↗

bioRxiv2018

The Warburg effect and lactate signaling augment Fgf signaling to promote sensory-neural development in the otic vesicle

Recent studies indicate that many developing tissues modify glycolysis to favor lactate synthesis, but how this promotes development is unclear. Using forward and reverse genetics in zebrafish, we show that disrupting the glycolytic gene phosphoglycerate kinase-1 (pgk1) impairs Fgf-dependent development of hair cells and neurons in the otic vesicle and other neurons in the CNS/PNS. Focusing on the otic vesicle, we found that Fgf signaling underperforms in pgk1-/- mutants even when Fgf is transiently overexpressed. Wild-type embryos treated with drugs that block synthesis or secretion of lactate mimic the pgk1-/- phenotype, whereas pgk1-/- mutants are rescued by treatment with exogenous lactate. Lactate treatment of wild-type embryos elevates expression of Etv5b/Erm even when Fgf signaling is blocked. Thus, by raising steady-state levels of Etv5b (a critical effector of the Fgf pathway), lactate renders cells more responsive to dynamic changes in Fgf signaling required by many developing tissues.

developmental biology↗