Biology subjects

Gallar, J.

Publications and source records attributed to Gallar, J..

2 recordsLinked to original sources

bioRxiv2025

In vivo Morphological Dynamics of Single Laser-Axotomized Corneal Nerve Fibers in Sarm1-Null Adult Mice

Axonal regeneration represents a pivotal aspect of the adult peripheral nervous system (PNS). When an injury occurs, peripheral axons are able to regenerate and reestablish connections with their original targets. Although several precision techniques for severing axons in various non-mammalian model organisms have allowed to study the dynamics of regeneration after injury, similar axonal injury models have yet to be fully developed in mammals. In this study, we introduced a novel experimental method for laser-induced axotomy of single corneal sensory subbasal nerve fibers. This method enables the in vivo monitoring and quantification of axonal degeneration and regeneration morphological dynamics in adult mice. Results revealed that the degeneration of the distal stump of the subbasal fiber was delayed in mice lacking the protein SARM1, which promotes degenerative process after injury. Meanwhile, the proximal stump maintained the regenerative dynamics of the subbasal fiber, but regeneration of its nerve terminals was impaired. The present study introduces a valuable model for the in vivo study of the morphological plasticity dynamics of peripheral axons after injury in genetically tractable adult mammals.

neuroscience↗

bioRxiv2021

A genetic compensatory mechanism regulated by c-Jun and Mef2d modulates the expression of distinct class IIa HDACs to ensure peripheral nerve myelination and repair

The class IIa histone-deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express HDAC4, 5 and 7 but not HDCA9. Here we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negative regulators of myelination ensuring peripheral nerve developmental myelination and remyelination after injury. Thus, when HDAC4 and 5 are knocked-out from Schwann cells, a c-Jun dependent mechanism induces the compensatory overexpression of HDAC7 permitting, although with a delay, the formation of a myelin sheath. When HDAC4,5 and 7 are simultaneously removed, the Myocyte- specific enhancer-factor d (Mef2d) binds to the promoter and induces the de novo expression of HDAC9, and although several melanocytic- lineage genes are mis- expressed and Remak bundle structure is disrupted, myelination proceeds after a long delay. Thus, our data unveil a finely tuned compensatory mechanism within the class IIa HDAC family, coordinated by distinct transcription factors, that guarantees the ability of Schwann cells to myelinate during development and remyelinate after nerve injury.

cell biology↗