Biology subjects

Elbaz, B.

Publications and source records attributed to Elbaz, B..

4 recordsLinked to original sources

bioRxiv2022

The canonical Wnt signaling pathway is not a promising therapeutic target for PNS regeneration enhancement

PNS injury initiates transcriptional changes in Schwann cells, satellite glial cells and PNS neurons that facilitate regeneration. The signaling pathways that control these transcriptional changes are not fully understood. The canonical Wnt signaling pathway is active during early stages of PNS development, where it controls radial axonal sorting and the onset of PNS myelination. Upon PNS injury, the Wnt signaling pathway is re-activated, suggesting that Wnt signaling plays an important role in PNS regeneration. To explore the potential of the Wnt pathway as a therapeutic target for enhancement of PNS recovery, we used a combination of genetic and pharmacological approaches to either activate or inhibit the Wnt signaling pathway during PNS recovery. We found that manipulating the Wnt signaling pathway does not alter PNS regeneration. Our data suggests that the Wnt signaling pathway is not a strong therapeutic target for the enhancement of PNS regeneration.

neuroscience↗

bioRxiv2021

Demyelination induces transcriptional reprogramming in proprioceptive and Aβ rapidly adapting low-threshold-mechanoreceptor neurons.

Schwann cells, the main glial cell in the peripheral nervous system (PNS), ensheath bundles of small unmyelinated axons or form myelin on larger axons. PNS injuries initiate transcriptional reprograming in both Schwann cells and sensory neurons that promotes regeneration. While the factors that initiate the transcriptional reprograming in Schwann cells are well characterized, the full range of stimuli that initiate this reprograming in sensory neurons remain elusive. Here, using a genetic model of Schwann cell ablation, we find that Schwann cell loss results in transient PNS demyelination without overt axonal loss. By profiling sensory ganglia at single-cell resolution we show that this demyelination induces transcriptional reprogramming preferably in proprioceptive and A{beta} RA-LTMR neurons. Transcriptional reprograming is assumed to be a cell autonomous response of sensory neurons to mechanical axonal injury. By identifying similar reprograming in non-injured, demyelinated neurons, our study suggests that this reprograming represents a non-cell autonomous transcriptional response of sensory neurons to the loss of axon-Schwann cell interactions. HighlightsO_LIAblation of Schwann cells results in transient PNS demyelination, without overt axonal loss. C_LIO_LISchwann cell loss results in transcriptional reprograming in specific sensory neurons. C_LIO_LISpinal nerve transection (mechanical injury of axons) and demyelination (intact axons) induces similar transcriptional responses in DRG neurons. C_LIO_LIThe transcriptional response to demyelination among DRG neurons is specific to the large myelinated proprioceptive and A{beta} RA-LTMR neurons. C_LI

neuroscience↗

bioRxiv2019

Silicon Nanowires for Intracellular Optical Interrogation with Sub-Cellular Resolution

Current techniques for intracellular electrical interrogation are substrate bound and are technically demanding, or lack high spatial resolution. In this work, we use silicon nanowires, which are spontaneously internalized by many cell types, to achieve photo-stimulation with sub-cellular resolution. Myofibroblasts loaded with silicon nanowires remain viable and can undergo cell division. Stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes. We also show that nanowire-containing myofibroblasts can electrically couple to cardiomyocytes in co-culture and that photo-stimulation of the nanowires increases the spontaneous activation rate in neighboring cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron-glia interactions using nanowire-containing oligodendrocytes.

bioengineering↗

bioRxiv2019

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

Nervous system function critically relies on continuous expression of neuron type-specific terminal identity features, such as neurotransmitter receptors, ion channels and neuropeptides. How individual neuron types select such features during development and maintain them throughout life is poorly understood. Here, we report an unconventional mechanism that enables cholinergic motor neurons (MNs) in the C. elegans ventral nerve cord to select and maintain their distinct terminal identity features. The conserved terminal selector UNC-3 (Collier/Ebf) UNC-3 is continuously required not only to promote cholinergic MN features, but also to prevent expression of \"unwanted\" terminal identity features normally reserved for other neuron types. Mechanistically, this dual function is achieved by the ability of UNC-3 to prevent a switch in the transcriptional targets of the Hox protein LIN-39 (Scr/Dfd/Hox4-5). The strategy of a terminal selector preventing a Hox transcriptional switch may constitute a general principle for safeguarding neuronal terminal identity features throughout life.

developmental biology↗